AMPK activator containing 1,1-diethoxyethane as an active ingredient and its use

Abstract

The present invention provides a pharmaceutical composition, cosmetic composition, food composition, or feed composition for the prevention, improvement, or treatment of obesity or related metabolic diseases, comprising 1,1-diethoxyethane (1,1-DEE) as an active ingredient. [Solution] The present invention provides an AMPK activator containing 1,1-DEE as an active ingredient, and its uses, for example, as a composition for preventing, treating or improving diseases requiring AMPK activation, anti-aging, life extension, or enhancing physical vitality, such as a pharmaceutical composition, cosmetic composition, food composition, or feed composition. The present invention also provides a composition for improving insulin resistance, or for preventing or treating obesity or related metabolic diseases, such as a pharmaceutical composition, cosmetic composition, food composition, or feed composition, containing 1,1-DEE as an active ingredient.

Description

【Technical Field】 【0001】 The present invention relates to an AMPK activator containing 1,1 - diethoxyethane (1,1 - DEE) as an active ingredient and its uses. More specifically, the present invention relates to an AMPK activator containing 1,1 - diethoxyethane as an active ingredient and its uses, for example, as a composition for preventing, treating or improving diseases that require AMPK activation, anti - aging, life - extension or physical vitality enhancement, in pharmaceutical compositions, cosmetic compositions, food compositions or feed compositions. 【0002】 The present invention also relates to a composition for improving insulin resistance containing 1,1 - diethoxyethane (1,1 - DEE) as an active ingredient and its uses. More specifically, the present invention relates to a composition for increasing insulin sensitivity or improving resistance containing 1,1 - diethoxyethane as an active ingredient as a PTEN oxidative inhibitor and its uses, for example, a composition for preventing, treating or improving diseases related to insulin resistance, in pharmaceutical compositions, cosmetic compositions, food compositions or feed compositions. 【0003】 The present invention also relates to a composition for preventing or treating obesity or related metabolic diseases containing 1,1 - diethoxyethane (1,1 - DEE) as an active ingredient. More specifically, the present invention relates to a pharmaceutical composition, cosmetic composition, food composition or feed composition for preventing or treating obesity containing 1,1 - diethoxyethane as an active ingredient. 【Background Art】 【0004】 AMPK activation 5'-adenosine monophosphate (AMP)-activated protein kinase (AMPK) is an evolutionarily conserved serine (Ser) / threonine (Thr) kinase enzyme responsible for maintaining cellular energy homeostasis and playing a crucial role in regulating energy balance [1,2]. AMPK consists of a catalytic α-subunit, a regulatory β-subunit, and a non-catalyzed γ-subunit, each of which regulates various physiological functions [3]. The α-subunit activates AMPK by phosphorylation of the Thr172 residue, the β-subunit promotes the binding of AMPK to glycogen, and the γ-subunit stimulates AMPK phosphorylation by binding to AMP and ADP [4]. AMPK activation promotes catabolic metabolism and inhibits anabolic metabolism to produce ATP and improve energy balance. Upstream kinases such as LKB1 (liver kinase B1), CAMKK2 (Ca2+ / calmodulin-dependent protein kinase kinase-2), and TAK (Transforming growth factor-beta-activated kinase) play important roles in AMPK activation [5-7]. Drugs such as metformin, AICAR (5-aminoimidazole-4-carboxamide ribonucleotide), and resveratrol activate AMPK by modulating upstream kinases [8-10]. Energy states such as exercise and nutritional deficiencies can also activate AMPK. AMPK activation may have potential effects in preventing obesity, cardiovascular disease (CVD), and cancer

[11] , and plays a particularly important preventive role in cardiovascular disease [12-17]. 【0005】 AMPK plays a crucial role in energy balance by regulating fatty acid synthesis and downstream effectors of catabolic processes such as glycolysis. Acetyl-CoA carboxylase (ACC) plays a vital role in fatty acid biosynthesis, and its enzymatic activity is suppressed by phosphorylation of Ser79 (ACC1) or Ser212 (ACC2) by AMPK, leading to increased fatty acid oxidation [1]. In the heart, fatty acid oxidation is a vital part of energy production. The AMPK-ACC signaling pathway regulates various physiological processes, including platelet phospholipid and thrombus formation, cardiac hypertrophy and contractility, and ischemia regulation [19-21]. Glycolysis is also regulated by PFKFB2 (6-phosphofructo-2-kinase / fructose-2,6-biphosphatase-2), which regulates the enzymatic activity of PFK1 (phosphofructokinase-1), involved in the formation and degradation of Fru-2,6-P2 (fructose-2,6-bisphosphate). Phosphorylation of PFKFB2 at Ser466 and Ser483 promotes glycolysis, which is regulated by Akt (protein kinase B) and AMPK. Activation of PFKFB2 plays an important role in cardiac remodeling, suppression of ferroptosis in I / R injury, and improvement of cardiac function in hypoxic conditions [22-24]. 【0006】 Mitochondrial biosynthesis is a crucial process for adapting to cellular energy needs, and AMPK can facilitate this process. AMPK deficiency can lead to mitochondrial dysfunction, and PGC-1α (peroxisome proliferator-activated receptor gamma coactivator 1-alpha), a major submodulator of AMPK, plays a vital role in mitochondrial biosynthesis [2]. AMPK activates PGC-1α via transcription factor EB activation and direct binding, and phosphorylates PGC-1α at Thr177 and Ser538 to promote mitochondrial biosynthesis [27, 28]. This process makes an important contribution to cardioprotection [29, 30]. 【0007】 Increased insulin sensitivity or resistance The PI3K / Akt (phosphoinositide-3-kinase / protein kinase B) pathway is a crucial signaling system that regulates various cellular processes such as proliferation, survival, and differentiation. When ligands such as growth factors bind to RTK (receptor tyrosine kinase), PI3K is activated, and PIP2 (phosphatidylinositol(4,5)-bisphosphate) is phosphorylated to PIP3 (phosphatidylinositol(3,4,5)-trisphosphate). When PIP3 accumulates on the cell membrane, Akt is activated, which regulates various downstream effectors. 【0008】 PTEN (phosphatase and tensin homolog deleted on chromosome 10) possesses lipid phosphate hydrolase function, dephosphorylating PIP3 to PIP2, and plays a crucial role as a negative regulator in the PI3K / Akt signaling pathway. PTEN is regulated by various post-translational modifications, and changes such as oxidation, acetylation, or s-nitrosylation can inhibit its lipid phosphate hydrolase function. For example, the catalytic nucleophile of PTEN, Cys124, is readily oxidized by reactive oxygen species (ROS), leading to the formation of a disulfide bond between Cys124 and Cys71, thereby suppressing PTEN function. 【0009】 Inhibition of PTEN increases PIP3 concentration, which can activate the PI3K / Akt pathway via Akt activation. This is expected to enhance insulin signaling and improve insulin sensitivity. This mechanism presents new possibilities in the treatment of metabolic diseases, and related research is actively progressing. 【0010】 The PI3K / Akt pathway plays a crucial role, particularly in regulating insulin sensitivity. When insulin binds to the transmembrane RTK (insulin receptor), the PI3K / Akt pathway is activated through an autophosphorylation process. This Akt activation promotes glycolysis and glycogen synthesis, increasing the intracellular influx and metabolism of glucose. 【0011】 obesity In modern society, while the economy is rapidly developing and nutritional intake is improving, physical activity is decreasing significantly. As a result, the prevalence of metabolic syndromes, characterized by the combined appearance of two or more diseases such as obesity, diabetes, hypertension, hypertriglyceridemia, hypercholesterolemia, and arteriosclerosis, is increasing. Cardiovascular disease and stroke resulting from these syndromes are increasing to the point where they account for the second and third leading causes of death in South Korea. These diseases manifest as symptoms of unbalanced metabolism, where metabolic waste products and toxins accumulate in the body, leading to a loss of bodily functions. Consequently, metabolic syndromes can develop into insulin resistance syndrome, potentially acting as a cause of cardiovascular and cerebrovascular diseases. 【0012】 Metabolic syndromes can cause damage to the coronary arteries, leading to heart disease and stroke; reduce the kidneys' ability to remove salt, causing hypertension; and increase the percentage of triglycerides, which contribute to cardiovascular disease. They can also increase the risk of blood clotting, increase insulin resistance in type 2 diabetes, and cause various other problems, including damage to the eyes, kidneys, and nerves. 【0013】 Effective drugs for treating metabolic syndromes have not yet been developed, and drugs used to treat diabetes, dyslipidemia, and hypertension are currently being used to treat metabolic syndromes. Drugs currently available for the treatment of metabolic syndromes include diabetes medications such as metformin, thiazolidinediones (TZD) family drugs, glucosidase inhibitors, and dipeptidyl peptidase-IV (DDP) inhibitors, along with antihypertensives and antihyperlipidemia drugs. However, there are limitations to fundamentally improving metabolic syndromes with these drugs. 【0014】 Factors known to directly or indirectly influence the causes and treatment of metabolic syndromes include exercise, dietary habits, body weight, blood glucose, triglycerides, cholesterol, insulin resistance, adiponectin, leptin, AMP-activated protein kinase (AMPK) activity, sex hormones such as estrogen, genetic factors, and malonyl-CoA levels in the body. 【0015】 Therefore, for the effective management and treatment of metabolic syndromes, it would be ideal to develop substances that can maintain normal blood glucose levels while simultaneously improving obesity, which is the underlying cause of metabolic syndromes. However, to date, research and development for such therapeutic agents have been insufficient. [Prior art documents] [Non-patent literature] 【0016】 [Non-Patent Document 1] Steinberg, GRand DG Hardie, New insights into activation and function of the AMPK. Nat Rev Mol Cell Biol, 2023.24(4):p.255-272. [Non-Patent Document 2] Herzig,S.and RJShaw,AMPK:guardian of metabolism and mitochondrial homeostasis.Nat Rev Mol Cell Biol,2018.19(2):p.121-135. 【Outdoor Tools3】 Davies,SP,et al.,Purification of the AMP-activated protein kinase on ATP-gamma-sepharose and analysis of its subunit structure.Eur J Biochem,1994.223(2):p.351-7. 【Outdoor Tools 4】 Hardie,DG,FARoss,and SAHawley,AMPK:a nutrient and energy sensor that maintains energy homeostasis.Nat Rev Mol Cell Biol,2012.13(4):p.251-62. 【Direct Environment 5】 Woods,A.,et al.,LKB1 is the upstream kinase in the AMP-activated protein kinase cascade.Curr Biol,2003.13(22):p.2004-8. 【Outdoor Configuration 6】 Woods,A.,et al.,Ca2+ / calmodulin-dependent protein kinase kinase-beta acts upstream of AMP-activated protein kinase in mammalian cells.Cell Metab,2005.2(1):p.21-33. 【Direct Environment 7】 Xie,M.,et al.,A pivotal role for endogenous TGF-beta-activated kinase-1 in the LKB1 / AMP-activated protein kinase energy-sensing pathway.Proc Natl Acad Sci USA,2006.103(46):p.17378-83. 【Outdoor Tools 8】 Shaw,RJ,et al.,The kinase LKB1 mediates glucose homeostasis in the liver and therapeutic effects of metformin.Science,2005.310(5754):p.1642-6. 【Outdoor Tools9】 Chan,AY,et al.,Resveratrol inhibits cardiac hypertrophy via AMP-activated protein kinase and Akt.J Biol Chem,2008.283(35):p.24194-201. 【Outdoor Tools 10】 Corton,JM,et al.,5-aminoimidazole-4-carboxamide ribonucleoside.A specific method for activating AMP-activated protein kinase in intact cells?Eur J Biochem,1995.229(2):p.558-65. 【Outdoor Content11】 Jeon, SM, Regulation and function of AMPK in physiology and diseases.Exp Mol Med,2016.48(7):p.e245. 【Outdoor Tools 12】 Li,Y.,et al.,AMPK phosphorylates and inhibits SREBP activity to attenuate hepatic steatosis and atherosclerosis in diet-induced insulin-resistant mice.Cell Metab,2011.13(4):p.376-388. 【Outdoor Tools13】 Pulipaka,S.,et al.,Therapeutic efficacies of mitochondria-targeted esculetin and metformin in the improvement of age-associated atherosclerosis via regulating AMPK activation.Geroscience,2024.46(2):p.2391-2408. 【Outdoor Tools 14】 Wang,Z.,et al.,Dexmedetomidine attenuates myocardial ischemia / reperfusion-induced ferroptosis via AMPK / GSK-3β / Nrf2 axis.Biomed Pharmacother,2022.154:p.113572. 【Outdoor Tools 15】 Zhang,Y.,et al.,Melatonin attenuates myocardial ischemia-reperfusion injury via improving mitochondrial fusion / mitophagy and activating the AMPK-OPA1 signaling pathways.J Pineal Res,2019.66(2):p.e12542. 【Outdoor Tools 16】 Gelinas, R., et al., AMPK activation counteracts cardiac hypertrophy by reducing O-GlcNAcylation. Nat Commun, 2018. 9(1): p. 374. 【Non-Patent Document 17】 Guo, R. and J. Ren, Deficiency in AMPK attenuates ethanol-induced cardiac contractile dysfunction through inhibition of autophagosome formation. Cardiovasc Res, 2012. 94(3): p. 480-91. 【Non-Patent Document 18】 Tong, L., Acetyl-coenzyme A carboxylase: crucial metabolic enzyme and attractive target for drug discovery. Cell Mol Life Sci, 2005. 62(16): p. 1784-803. 【Non-Patent Document 19】 Lepropre, S., et al., AMPK-ACC signaling modulates platelet phospholipids and potentiates thrombus formation. Blood, 2018.  132(11): p. 1180-1192. 【Non-Patent Document 20】 Turdi, S., et al., Deficiency in AMP-activated protein kinase exaggerates high fat diet-induced cardiac hypertrophy and contractile dysfunction. J Mol Cell Cardiol, 2011. 50(4): p. 712-22. 【Non-Patent Document 21】 Hopkins,TA,JRDyck,and GDLopaschuk,AMP-activated protein kinase regulation of fatty acid oxidation in the ischemic heart.Biochem Soc Trans,2003.31(Pt 1):p.207-12. 【Optional Website22】 Harold,KM,et al.,Loss of Cardiac PFKFB2 Drives Metabolic、Functional,and Electrophysiological Remodeling in the Heart.J Am Heart Assoc,2024.13(7):p.e033676. 【Optional Trademark23】 Fu,C.,et al.,PFKFB2 Inhibits Ferroptosis in Myocardial Ischemia / Reperfusion Injury Through Adenosine Monophosphate-Activated Protein Kinase Activation.J Cardiovasc Pharmacol,2023.82(2):p.128-137. 【Optional Trademark24】 Gao,J.,et al.,HIF-1 / AKT Signaling-Activated PFKFB2 Alleviates Cardiac Dysfunction and Cardiomyocyte Apoptosis in Response to Hypoxia.Int Heart J,2021.62(2):p.350-358. 【Direct Entries 25】 Bergeron,R.,et al.,Chronic activation of AMP kinase results in NRF-1 activation and mitochondrial biogenesis.Am J Physiol Endocrinol Metab,2001.281(6):p.E1340-6. [Non-Patent Document 26] Lantier, L., et al., AMPK controls exercise endurance, mitochondrial oxidative capacity, and skeletal muscle integrity. Faseb j, 2014.28(7):p.3211-24. [Non-Patent Document 27] Settembre, C., et al., TFEB controls cellular lipid metabolism through a starvation-induced autoregulatory loop. Nat Cell Biol, 2013.15(6):p.647-58. [Non-Patent Document 28] Jager, S., et al., AMP-activated protein kinase(AMPK) action in skeletal muscle via direct phosphorylation of PGC-1alpha.Proc Natl Acad Sci USA, 2007.104(29):p.12017-22. [Non-Patent Document 29] Chen, L., et al., PGC-1α-Mediated Mitochondrial Quality Control: Molecular Mechanisms and Implications for Heart Failure.Front Cell Dev Biol,2022.10:p.871357. [Non-Patent Document 30] Tian, ​​L., et al., Pretreatment with Tilianin improves mitochondrial energy metabolism and oxidative stress in rats with myocardial ischemia / reperfusion injury via AMPK / SIRT1 / PGC-1 alpha signaling pathway.J Pharmacol Sci,2019.139(4):p.352-360. [Overview of the project] [Problems that the invention aims to solve] 【0017】 The inventors diligently studied the physiological function of 1,1-diethoxyethane (1,1-DEE) and confirmed that 1,1-DEE reversibly activates AMPK (AMP-activated protein kinase) within 5-10 minutes by phosphorylating the Ser172 residue, and that its efficacy can be further enhanced through a partially reactive oxygen species (ROS)-dependent mechanism. Furthermore, they confirmed that long-term exposure of cells to 1,1-DEE resulted in sustained AMPK activation and increased expression of PGC-1α, a gene associated with mitochondrial metabolism. This demonstrates that 1,1-DEE can simultaneously provide acute and long-term activating effects on AMPK. 【0018】 Therefore, the present invention aims to provide an AMPK (AMP-activated protein kinase) activator containing 1,1-diethoxyethane (1,1-DEE) as an active ingredient, and a pharmaceutical composition, cosmetic composition, food composition, or feed composition for the prevention, improvement, or treatment of diseases requiring AMPK (AMP-activated protein kinase) activation, as well as for anti-aging, life extension, or enhancement of physical vitality. 【0019】 Furthermore, the inventors diligently studied the physiological function of 1,1-diethoxyethane (1,1-DEE) and confirmed that 1,1-DEE induces oxidative inactivation of PTEN (phosphatase and tensin homolog deleted on chromosome 10) through the formation of a disulfide bond between Cys124 and Cys71 residues. This oxidative inactivation of PTEN induces increased phosphorylation of Akt at Ser473 and Thr308, thereby activating Akt. This Akt activation increases phosphorylation at Ser483 of PFKFB2 (6-phosphofructo-2-kinase / fructose-2,6-biphosphatase 2), thereby promoting the rate of glycolysis. Furthermore, we confirmed that combined treatment with 1,1-DEE and insulin not only increases Akt activation and improves insulin sensitivity, but that 1,1-DEE can also mitigate palmitic acid-induced insulin resistance. 【0020】 Therefore, the present invention aims to provide a composition for increasing insulin sensitivity or improving insulin resistance containing 1,1-diethoxyethane (1,1-DEE) as an active ingredient, a pharmaceutical composition, cosmetic composition, food composition or feed composition for preventing, improving or treating diseases related to insulin resistance containing 1,1-diethoxyethane (1,1-DEE) as an active ingredient. 【0021】 Furthermore, the inventors investigated the effects of 1,1-diethoxyethane (1,1-DEE) on weight gain, blood glucose regulation, insulin resistance, liver damage, and fat production in obesity and metabolic disease models induced by a high-fat diet (HFD). The results showed that 1,1-DEE suppressed weight gain, improved blood glucose and insulin resistance, alleviated liver damage and fat production, and reduced the amount of LDL cholesterol in the blood in 1,1-DEE mice. 【0022】 Therefore, the present invention aims to provide a pharmaceutical composition, cosmetic composition, food composition, or feed composition for the prevention, improvement, or treatment of obesity or related metabolic diseases, comprising 1,1-diethoxyethane (1,1-DEE) as an active ingredient. 【0023】 However, the problems that this application seeks to solve are not limited to those mentioned above, and other problems not mentioned will be clearly understood by those skilled in the art from the following description. [Means for solving the problem] 【0024】 The present invention discloses a composition containing 1,1-diethoxyethane (1,1-DEE) as an active ingredient, which may be a pharmaceutical composition, a cosmetic composition, a food composition, or a feed composition. 【0025】 In the present invention, the 1,1-diethoxyethane (1,1-diethoxyethane, 1,1-DEE) has the molecular formula C6H 14 It is represented by the following structural formula 1 with O2, and is also called acetaldehyde diethyl acetal or ethyllidene diethyl ether. 【0026】 [ka] 【0027】 1. AMKP activator According to one example, An AMPK (AMP-activated protein kinase) activator containing 1,1-diethoxyethane (1,1-DEE) as an active ingredient is disclosed. 【0028】 In the present invention, the 1,1-diethoxyethane can induce phosphorylation of the Ser172 residue of AMPK, thereby promoting fatty acid oxidation and regulating glycolysis. 【0029】 In the present invention, the 1,1-diethoxyethane can temporarily suppress oxidative phosphorylation (OXPHOS) and activate AMPK through the production of ROS (reactive oxygen species). 【0030】 In the present invention, the 1,1-diethoxyethane can increase PGC-1α (peroxisome proliferator-activated receptor gamma coactivator-1 alpha) expression and promote mitochondrial biosynthesis. 【0031】 According to other implementation examples, A pharmaceutical composition containing 1,1-diethoxyethane (1,1-DEE) as an active ingredient is disclosed for the prevention or treatment of diseases requiring AMPK (AMP-activated protein kinase) activation, as well as for anti-aging, life extension, or enhancement of physical vitality. 【0032】 In the present invention, the diseases requiring AMPK activation may include one or more selected from metabolic disorders such as diabetes, obesity, nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), liver fibrosis, and dyslipidemia; cardiovascular diseases such as atherosclerosis, hypertension, heart failure, and ischemic heart disease; neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease; inflammatory diseases such as inflammatory bowel disease and rheumatoid arthritis; leukemia; and cancer. 【0033】 In the present invention, the enhancement of physical vitality may include one or more selected from the following: enhancement of immunity, improvement of physical strength, improvement of physical endurance, increase of energy levels, increase of vitality, enhancement of physical recovery ability, or support for sustained physical activity. 【0034】 In the present invention, the pharmaceutical composition may be administered by one or more methods selected from the group consisting of oral administration, intravenous injection, subcutaneous injection, intramuscular injection, intraperitoneal injection, epithelial administration, local administration, vaginal administration, pulmonary administration, rectal administration, sublingual administration, buccal administration, transdermal administration, ocular administration, inhalation, intracavernosal injection, intrathecal injection, epidural injection, and rectal injection. 【0035】 According to other implementation examples, A cosmetic composition containing 1,1-diethoxyethane (1,1-DEE) as an active ingredient is disclosed for the prevention or improvement of diseases requiring AMPK (AMP-activated protein kinase) activation, as well as for anti-aging, life extension, or enhancement of physical vitality. 【0036】 In the present invention, the cosmetic composition can be formulated into one or more of the following: a solution, an external ointment, a cream, a foam, a nourishing lotion, a softening lotion, a perfume, a pack, a softening water, an emulsion, a makeup base, an essence, a soap, a liquid cleanser, a bath additive, a sunscreen cream, a sun oil, a suspension, an emulsion, a paste, a gel, a lotion, a powder, a soap, a surfactant-containing cleanser, an oil, a powder foundation, an emulsion foundation, a wax foundation, a patch, and a spray. 【0037】 According to other implementation examples, A food composition containing 1,1-diethoxyethane (1,1-DEE) as an active ingredient is disclosed for the prevention or improvement of diseases requiring AMPK (AMP-activated protein kinase) activation, as well as for anti-aging, life extension, or enhancement of physical vitality. 【0038】 In the present invention, the food may include meats, sausages, bread, chocolates, candies, snacks, confectionery, pizzas, ramen noodles, other noodle products, gums, dairy products including ice cream, various soups, drinking water, tea, coffee beverages, energy drinks, alcoholic beverages, or vitamin complexes. 【0039】 According to other implementation examples, A feed composition containing 1,1-diethoxyethane (1,1-DEE) as an active ingredient is disclosed for the prevention or improvement of diseases requiring AMPK (AMP-activated protein kinase) activation, as well as for anti-aging, life extension, or enhancement of physical vitality. 【0040】 In the present invention, the feed may include powdered feed, solid feed, moist pellet feed, dry pellet feed, EP (Extruder Pellet) feed, or raw feed. 【0041】 2. Compositions for increasing insulin sensitivity or improving insulin resistance According to one example, A composition for increasing insulin sensitivity or improving insulin resistance is disclosed, comprising 1,1-diethoxyethane (1,1-DEE) as an active ingredient. 【0042】 In the present invention, the 1,1-diethoxyethane can induce oxidative inactivation of PTEN through the formation of a disulfide bond between the Cys124 and Cys71 residues of PTEN. 【0043】 In the present invention, the 1,1-diethoxyethane can activate Akt by increasing phosphorylation at Ser473 and Thr308 of Akt. 【0044】 In the present invention, the 1,1-diethoxyethane can promote glycolysis by increasing phosphorylation at the Ser483 residue of PFKFB2 (6-phosphofructo-2-kinase / fructose-2,6-biphosphatase 2). 【0045】 According to other implementation examples, A pharmaceutical composition for the prevention or treatment of insulin resistance-related diseases is disclosed, comprising 1,1-diethoxyethane (1,1-DEE) as an active ingredient. 【0046】 In the present invention, the diseases related to insulin resistance include metabolic disorders such as Type 1 diabetes, Type 2 diabetes, Impaired Glucose Tolerance (IGT), Impaired Fasting Glucose (IFG), Hyperglycemia, Postprandial Hyperglycemia, Polycystic Ovary Syndrome (PCOS), Hyperlipidemia, Hypertension, Overweight, Obesity, and Metabolic Syndrome; Fasting Plasma Glucose (FPG), Postprandial Plasma Glucose dysregulation, including a decrease in glucose (PPG) and / or glycated hemoglobin (HbA1c) and improved blood glucose control; diabetes progression-related disorders, including prevention, slowing, delaying, or reversal of progression from impaired glucose tolerance (IGT), impaired fasting glucose (IFG), insulin resistance, or metabolic syndrome to type 2 diabetes;Diabetic complications including cataracts, microvascular and macrovascular diseases, nephropathy, retinopathy, neuropathy, tissue ischemia, diabetic foot disease, atherosclerosis, myocardial infarction, acute coronary syndrome, unstable angina, stable angina, stroke, peripheral artery occlusive disease, cardiomyopathy, heart failure, cardiac arrhythmia, and vascular restenosis; weight loss, prevention of weight gain, or promotion of weight loss. This may include one or more of the following: weight management disorders, including weight loss; pancreatic beta-cell related disorders, including prevention, slowing, delaying, or treating pancreatic beta-cell degeneration and / or beta-cell dysfunction, improvement and / or restoration of pancreatic beta-cell function, and / or restoration of pancreatic insulin secretion function; liver diseases, including prevention, slowing, delaying, or treating diseases or conditions due to abnormal accumulation of liver fat; and insulin-related disorders, including maintenance and / or improvement of insulin sensitivity, and prevention or treatment of hyperinsulinemia and / or insulin resistance. 【0047】 In the present invention, the pharmaceutical composition may be administered by one or more methods selected from the group consisting of oral administration, intravenous injection, subcutaneous injection, intramuscular injection, intraperitoneal injection, epithelial administration, local administration, vaginal administration, pulmonary administration, rectal administration, sublingual administration, buccal administration, transdermal administration, ocular administration, inhalation, intracavernosal injection, intrathecal injection, epidural injection, arterial injection, lymphatic administration, intraosseous injection, and drug administration via the lacrimal duct. 【0048】 According to other implementation examples, A cosmetic composition for the prevention or improvement of insulin resistance-related diseases is disclosed, comprising 1,1-diethoxyethane (1,1-DEE) as an active ingredient. 【0049】 In the present invention, the cosmetic composition can be formulated into one or more of the following: a solution, an external ointment, a cream, a foam, a nourishing lotion, a softening lotion, a perfume, a pack, a softening water, an emulsion, a makeup base, an essence, a soap, a liquid cleanser, a bath additive, a sunscreen cream, a sun oil, a suspension, an emulsion, a paste, a gel, a lotion, a powder, a soap, a surfactant-containing cleanser, an oil, a powder foundation, an emulsion foundation, a wax foundation, a patch, and a spray. 【0050】 According to other implementation examples, A food composition for the prevention or improvement of insulin resistance-related diseases is disclosed, comprising 1,1-diethoxyethane (1,1-DEE) as an active ingredient. 【0051】 In the present invention, the food may include meats, sausages, bread, chocolates, candies, snacks, confectionery, pizzas, ramen noodles, other noodle products, gums, dairy products including ice cream, various soups, drinking water, tea, coffee beverages, energy drinks, alcoholic beverages, or vitamin complexes. 【0052】 According to other implementation examples, A feed composition for the prevention or improvement of insulin resistance-related diseases is disclosed, comprising 1,1-diethoxyethane (1,1-DEE) as an active ingredient. In the present invention, the feed may include powdered feed, solid feed, moist pellet feed, dry pellet feed, EP (Extruder Pellet) feed, or raw feed. 【0053】 3. Compositions for the prevention, improvement, or treatment of obesity or related metabolic diseases According to one example, A pharmaceutical composition for the prevention or treatment of obesity or related metabolic diseases, comprising 1,1-diethoxyethane as an active ingredient, is disclosed. In the present invention, the obesity-related metabolic diseases may include type 2 diabetes, fatty liver, hyperlipidemia, hypertension, insulin resistance, arteriosclerosis, stroke, polycystic ovary syndrome (PCOS), metabolic syndromes, inflammatory bowel disease (IBD), and sleep apnea. 【0054】 In the present invention, the pharmaceutical composition may be administered by one or more methods selected from the group consisting of oral administration, intravenous injection, subcutaneous injection, intramuscular injection, intraperitoneal injection, epithelial administration, local administration, vaginal administration, pulmonary administration, rectal administration, sublingual administration, buccal administration, transdermal administration, ocular administration, inhalation, intracavernosal injection, intraspinal injection, epidural injection, oral mucosal administration, intrabronchial administration, intralymphatic administration, head and neck administration, and intracardiac administration. In the present invention, the pharmaceutical composition can be supported on a delivery body, and the delivery body may contain one or more selected from viral particles, vesicles, nanoparticles, microparticles, liposomes, transposons, micelles, antibodies, and exosomes. 【0055】 According to other implementation examples, A cosmetic composition for preventing or improving cellulite is disclosed, comprising 1,1-diethoxyethane (1,1-DEE) as an active ingredient. In the present invention, the cosmetic composition can be formulated into one or more of the following: a solution, an external ointment, a cream, a foam, a nourishing lotion, a softening lotion, a perfume, a pack, a softening water, an emulsion, a makeup base, an essence, a soap, a liquid cleanser, a bath additive, a sunscreen cream, a sun oil, a suspension, an emulsion, a paste, a gel, a lotion, a powder, a soap, a surfactant-containing cleanser, an oil, a powder foundation, an emulsion foundation, a wax foundation, a patch, and a spray. 【0056】 According to other implementation examples, A food composition for the prevention or improvement of obesity or related metabolic diseases is disclosed, comprising 1,1-diethoxyethane (1,1-DEE) as an active ingredient. In the present invention, the obesity-related metabolic diseases may include type 2 diabetes, fatty liver, hyperlipidemia, hypertension, insulin resistance, arteriosclerosis, stroke, polycystic ovary syndrome (PCOS), metabolic syndromes, inflammatory bowel disease (IBD), and sleep apnea. In the present invention, the food may include meats, sausages, bread, chocolates, candies, snacks, confectionery, pizzas, ramen, other noodle products, gums, dairy products including ice cream, various soups, drinking water, tea, coffee beverages, energy drinks, alcoholic beverages, vitamin complexes, fruit juices, desserts, health supplements, instant foods, seasonings and sauces, and processed meat products. 【0057】 According to other implementation examples, A feed composition for the prevention or improvement of obesity or related metabolic diseases is disclosed, comprising 1,1-diethoxyethane (1,1-DEE) as an active ingredient. In the present invention, the obesity-related metabolic diseases may include type 2 diabetes, fatty liver, hyperlipidemia, hypertension, insulin resistance, arteriosclerosis, stroke, polycystic ovary syndrome (PCOS), metabolic syndromes, inflammatory bowel disease (IBD), and sleep apnea. In the present invention, the feed may include powdered feed, solid feed, moist pellet feed, dry pellet feed, EP (Extruder Pellet) feed, wet feed, treats, special feed, functional feed, dried feed, rice and grain feed, natural food feed, or raw feed. [Effects of the Invention] 【0058】 The 1,1-diethoxyethane (1,1-DEE) according to the present invention can provide the following effects. 【0059】 (1) 1,1-diethoxyethane can rapidly and reversibly activate AMPK through ATP reduction and ROS production. Activated AMPK can suppress fatty acid synthesis via ACC phosphorylation, promote β-oxidation, and regulate glycolysis via PFKFB2 phosphorylation. By activating AMPK, 1,1-diethoxyethane can increase PGC-1α expression, thereby enhancing mitochondrial biosynthesis and energy metabolism. Therefore, the 1,1-diethoxyethane according to the present invention is expected to be effective not only in preventing, treating, or improving diseases requiring AMPK activation, but also in being usefully utilized as a pharmaceutical composition, cosmetic composition, food composition, or feed composition for anti-aging, life extension, and enhancement of physical vitality. 【0060】 (2) 1,1-diethoxyethane induces oxidative inactivation of PTEN, thereby increasing Akt activation and increasing Ser483 phosphorylation of PFKFB2, which can promote glycolysis. 1,1-diethoxyethane can improve insulin sensitivity and improve palmitate-induced insulin resistance. Therefore, the 1,1-diethoxyethane according to the present invention is expected to be useful as a pharmaceutical composition, cosmetic composition, food composition, or feed composition for the prevention, treatment, or improvement of diseases related to insulin resistance. 【0061】 (3) 1,1-diethoxyethane was found to reduce weight gain and improve fat accumulation in eWAT and iWAT in obese mice fed a high-fat diet (HFD). Furthermore, 1,1-DEE was found to improve glucose tolerance and enhance insulin sensitivity. 1,1-diethoxyethane was found to reduce ALT, AST, and LHD, which are HFD-induced liver injury biomarkers, and to improve TG and LDL-C levels, thereby reducing the risk of fat accumulation and arteriosclerosis. Therefore, compositions containing 1,1-diethoxyethane according to the present invention are expected to be useful as pharmaceutical compositions, food compositions, cosmetic compositions, or feed compositions for the prevention, treatment, or improvement of obesity, diabetes, fatty liver, and related metabolic diseases. 【0062】 On the other hand, the scope of the present invention is not limited by the effects described above. [Brief explanation of the drawing] 【0063】 [Figure 1] 1. Reversible inhibitory effect of 1,1-DEE on oxygen consumption rate and cellular glycolysis in AC16 cells after acute exposure: (A) 2D structure of 1,1-DEE. (B) Viability assay of AC16 cells using EZ-Cytox reagent after 24 hours of culture with specified concentrations of 1,1-DEE. (C) Mitochondrial respiration was evaluated using the Agilent Seahorse XF96 Cell Mito Stress Test Kit after acute exposure to 1,1-DEE, metformin, and 1,2-DEE for 30 minutes. OCR was measured after sequential addition of various concentrations of 1,1-DEE, 1.5 μM oligomycin (oligo), 1.5 μM FCCP, and 0.5 μM rotenone / antimycin (R / A). (D) Proton leakage, ATP production, maximal respiration, and reserve respiratory capacity were measured using the Seahorse XF96 Cell Mito Stress Test Kit. (E) ECAR was measured under the conditions mentioned in (C). [Figure 2]This study demonstrates the concentration- and time-dependent activation of AMPK following acute exposure to 1,1-DEE. Western blot analysis of AC16 cells was performed to evaluate AMPK phosphorylation under the following conditions: (A) cultured with various concentrations of 1,1-DEE for 10 minutes, (B) cultured with 15 mM 1,1-DEE for 30 minutes, (C) cultured with 15 mM 1,2-DEE for 30 minutes, and (D) cultured with 15 mM metformin for 60 minutes. [Figure 3] The effects of AMPK activation on fatty acid oxidation and glycolysis after acute exposure to 1,1-DEE are demonstrated: (A) AC16 cells were exposed to 15 mM 1,1-DEE for 30 minutes. Phosphorylation of AMPK, ACC, and PFKFB2 was evaluated by Western blot analysis. (B) AC16 cells were exposed to 15 mM 1,1-DEE for 8 hours. mRNA expression levels of SREBP-1c and FASN were evaluated using semi-quantitative PCR and qRT-PCR. (C) WT and AMPK DKO MEF cells were exposed to 15 mM 1,1-DEE for 30 minutes. (D) AC16 cells were pretreated with 10 μM compound C for 1 hour and then cultured with 15 mM 1,1-DEE for 120 minutes. Western blot analysis was performed to evaluate phosphorylation of AMPK effectors, including ACC and PFKFB2. [Figure 4] This study demonstrates that AMPK activation may be partially mediated by 1,1-DEE-induced ROS production. AC16 cells were pretreated with 10 mM NAC for 2 hours or 10 μM ebselen for 1 hour, and then exposed to 15 mM 1,1-DEE for 30 minutes. Immunofluorescence staining with DCFH-DA was performed to observe ROS production, and Western blotting was performed to evaluate AMPK activation by phosphorylation in the Thr172 residue. [Figure 5]This study demonstrates that long-term exposure to 1,1-DEE can increase PGC-1α expression via AMPK activation. (AC) AC16 cells were cultured with 15 mM 1,1-DEE for up to 8 hours: (A) AMPK phosphorylation was evaluated by Western blot analysis. (B) PPARGC1A mRNA expression levels were analyzed by RT-PCR. (C) PGC-1α protein expression levels were confirmed by Western blot analysis. (D) MEF cells were cultured with 15 mM 1,1-DEE for up to 12 hours, after which AMPK phosphorylation and PGC-1α expression were evaluated by Western blot analysis. [Figure 6] This study demonstrates that PGC-1α-mediated AMPK activation can promote mitochondrial biosynthesis. (AB) AC16 cells were cultured with 15 mM 1,1-DEE for up to 8 hours: (A) mRNA expression levels of Nrf1, Nrf2, and Tfam were evaluated by real-time PCR. (B) Protein expression levels of Nrf1, Nrf2, and Tfam were analyzed by Western blotting. (C) WT and AMPK DKO MEF cells were cultured with 15 mM 1,1-DEE for up to 8 hours, and then the protein expression levels of Nrf1, Nrf2, and Tfam were confirmed by Western blotting. (D) AC16 cells were pretreated with compound C (10 μM) for 4 hours, then exposed to 15 mM 1,1-DEE for 24 hours, and the protein expression level of Tfam was evaluated by Western blotting. (E) AC16 cells were pretreated with compound C (10 μM) for 4 hours, then exposed to 15 mM 1,1-DEE for 8 hours, and stained with MitoTrackerRedCMXRos (200 nM) for 30 minutes. Mitochondrial biosynthesis was evaluated at 40x magnification through a confocal microscope. (F) Flow cytometry of AC16 cells was performed under the same conditions as in (E). [Figure 7]Showing 1,1-DEE confirmed in various ethanol batches: (A) HepG2 cells treated with 100 mM E1, E2, or E3 for 10 minutes. (B) Flowchart of the lyophilization process with 100 mM E1, E2, and E4. (C) Cells treated with 100 mM E1, E2, or E4 or the glycolysis lyophilized sample described in (B) for 10 minutes. After treatment, cell extracts were alkylated with 10 mM NEM, followed by non-reducing or reducing electrophoresis and staining with PTEN and β-actin antibodies. (D) Presence and chemical structure of 1,1-DEE confirmed by GC-MS analysis of E1. [Figure 8] This study demonstrates that 1,1-DEE can induce PTEN oxidation in a concentration-dependent manner: (A) C2C12, MEF, AC16, and Ea.hy926 cells were treated with various concentrations of 1,1-DEE (0-50 mM) for 10 minutes. (B) C2C12 cells were treated with the same concentrations of 1,2-DEE as in (A). After alkylating the cell lysates with 10 mM NEM, Western blotting was performed to confirm the PTEN oxidation level using PTEN and GAPDH antibodies. (C) HepG2 cells were transfected with HA-tagged pCGN PTEN WT, C71S, C124S, or C71S / C124S. After transfection, cells were treated with 10 mM 1,1-DEE for 10 minutes. After treatment, cells were lysed, alkylated with 10 mM NEM, and then immunoblotted with antibodies against the HA-tag. [Figure 9] This study demonstrates that 1,1-DEE can induce PTEN oxidation in a time-dependent manner: (A) C2C12, MEF, AC16, and EA.hy926 cells were treated with 10 mM 1,1-DEE for 120 minutes at various time intervals. (B) C2C12 cells were treated with 10 mM 1,2-DEE under the same conditions as in (A). After alkylation of the cell lysates with 10 mM NEM, reductive or non-reductive electrophoresis was performed, and immunoblotting analysis was carried out using PTEN antibodies. [Figure 10]This study demonstrates that PTEN oxidation induced by 1,1-DEE can activate the Akt signaling pathway: (A) C2C12 cells were treated with various concentrations of 1,1-DEE for 10 minutes. (B) C2C12 cells were treated with 10 mM 1,1-DEE at various time intervals for 120 minutes. Immunoblot analysis was performed using cell lysates with antibodies against phosphorylated Akt and total Akt at Ser473 and Thr308. [Figure 11] This study demonstrates that PTEN oxidation induced by 1,1-DEE is mediated by ROS production: (A) HepG2 cells were treated with 10 mM 1,1-DEE or 0.5 mM H2O2 for 10 minutes. The cells were then stained with 10 μM DCFH-DA for 30 minutes, and representative images of the stained cells were obtained using a fluorescence microscope (10x magnification). (B) HepG2 cells were treated with 0.5 mM H2O2 for 10 minutes or with 10 mM 1,1-DEE for 30 minutes at various time intervals. The cells were then stained with 10 μM DCFH-DA, and flow cytometry was performed using a FITC channel at 10,000 events per sample. (C) HepG2 cells were pretreated with 10 mM NAC for 120 minutes, and then treated with 10 mM 1,1-DEE for 120 minutes at various time intervals. Cell lysates were alkylated with 10 mM NEM, followed by non-reductive or reductive immunoblotting, and analyzed using antibodies against PTEN, phosphorylated Akt, Akt, and GAPDH. [Figure 12] This study demonstrates that 1,1-DEE can promote glycolysis through Akt activation: (A) AC16 cells were pretreated with 10 μM MK-2206 for 24 hours, followed by treatment with 10 mM 1,1-DEE for 30 minutes. (B) AC16 cells were pretreated with 10 μM Ebselen for 60 minutes, followed by treatment with 10 mM 1,1-DEE for 30 minutes at various time intervals. Cell lysates were alkylated with 10 mM NEM, and then Western blot analysis was performed using antibodies against PTEN, phosphorylated Akt, Akt, phosphorylated PFKFB2, PFKFB2, and GAPDH. [Figure 13]This study demonstrates that 1,1-DEE can improve insulin sensitivity and mitigate palmitic acid-induced insulin resistance: (A) C2C12 cells were treated with various concentrations of 1,1-DEE (0-10 mM) for 10 minutes with or without 20 nM insulin. (B) C2C12 cells were pretreated with 500 μM palmitic acid for 24 hours, then treated with 10 mM 1,1-DEE, 20 nM insulin, or both in parallel for 10 minutes. Cell lysates were alkylated with 10 mM NEM and then analyzed by Western blotting using antibodies against PTEN, phosphorylated Akt, Akt, and GAPDH. [Figure 14] This document outlines a protocol for creating an HFD-induced obesity model and a 1,1-DEE administration plan. [Figure 15] This study evaluated the effects of 1,1-DEE on body weight change and fat accumulation in an obesity model induced by high-fiber denaturation (HFD). The results are shown for (A) representative mice in each treatment group, (B) body weight change, (C) food intake change, (D) eWAT fat accumulation change, (E) iWAT fat accumulation change, (F) cardiac weight change, (G) liver weight change, and colon length change. [Figure 16] 1,1-DEE showed an effect of suppressing weight gain in HFD mice. Eight-week-old male mice were divided into six groups and given different diets to each group. The groups were as follows: ND (normal diet), ND+1,1-DEE (1,1-DEE 100 mg / kg treatment), HFD (high-fat diet), HFD+1,1-DEE (1,1-DEE 100 mg / kg treatment), HFD+Met (metaformin 100 mg / kg treatment), and HFD+1,2-DEE (1,2-DEE 100 mg / kg treatment) (n=7 in each group). After 4 weeks of treatment, the following parameters were measured: (A) weight change over 4 weeks in each treatment group, (B) weight comparison at week 12, and (C) food intake. Data are expressed as mean ± SEM, and statistical significance was assessed using an unpaired two-tailed Student's t-test (nsp > 0.05, **p ≤ 0.01). [Figure 17]This study evaluated the effects of 1,1-DEE on blood glucose levels and insulin sensitivity in obese mice induced by high-fiber dysplasia (HFD). The results are shown as follows: (A) data on random blood glucose changes, (B) changes in fasting blood glucose levels, (C) glucose tolerance test results, (D) changes in serum insulin levels, and (E) insulin tolerance test results. [Figure 18] This study evaluated the effect of 1,1-DEE on improving liver damage and fat production in HFD-induced obese mice. The results for (A) changes in ALT levels, (B) changes in AST levels, (C) changes in LHD levels, (D) changes in ALP levels, (E) changes in T-Bil levels, (F) changes in Ab levels, (G) changes in TG levels, (H) changes in T-chol levels, (I) changes in HDL-C levels, (J) changes in LDL-C levels, and (K) changes in LDL-C levels are shown below. [Modes for carrying out the invention] 【0064】 The following describes in detail specific examples of the present invention, including an AMPK activator containing 1,1-diethoxyethane as an active ingredient, a composition for increasing insulin sensitivity or improving insulin resistance containing 1,1-diethoxyethane as an active ingredient, or a composition for preventing or treating obesity or related metabolic diseases containing 1,1-diethoxyethane as an active ingredient, and their uses. However, this is merely one example of the invention and does not limit the scope of the invention, and it will be obvious to those skilled in the art that various modifications to the examples are possible within the scope of the invention. Unless otherwise specified herein, "contains" or "includes" means including a certain component (or constituent) without particular limitation and should not be construed as excluding the addition of other components (or constituents). 【0065】 As used herein, the term “treatment” means any form of therapy or prevention that provides an effect to an individual suffering from or at risk of developing a disease, including improvement of the individual’s condition, delay of disease progression, delay of symptom onset, or slowing of symptom progression. Accordingly, the term “treatment” includes prophylactic treatment of an individual that prevents the onset of symptoms. Furthermore, “treatment” and “prevention” are not intended to mean a cure or complete elimination of symptoms. 【0066】 As used herein, the term “improvement” may mean any action that reduces, for example, the degree of a condition or treatment, such as any action that at least reduces the severity of the symptoms. 【0067】 As used herein, the term "subject" means an animal, including animals such as cattle, monkeys, horses, sheep, pigs, chickens, turkeys, quail, cats, dogs, mice, rats, rabbits, or guinea pigs. For example, the subject may be a mammal, in particular a human. 【0068】 1. AMPK activator The present invention The aim is to provide an AMPK (AMP-activated protein kinase) activator containing 1,1-diethoxyethane (1,1-DEE) as an active ingredient. 【0069】 In the AMPK activator according to the present invention, the 1,1-diethoxyethane can induce phosphorylation of the Ser172 residue of AMPK, thereby promoting fatty acid oxidation and regulating glycolysis. 【0070】 In the AMPK activator according to the present invention, the 1,1-diethoxyethane can suppress oxidative phosphorylation (OXPHOS) and activate AMPK by mediating ROS (reactive oxygen species) production. 【0071】 In the AMPK activator according to the present invention, the 1,1-diethoxyethane can increase PGC-1α (peroxisome proliferator-activated receptor gamma coactivator-1 alpha) expression and promote mitochondrial biosynthesis. 【0072】 In the AMPK activator according to the present invention, the 1,1-diethoxyethane can induce phosphorylation of ACC (acetyl-CoA carboxylase) in mitochondria, thereby reducing malonyl-CoA production. 【0073】 The AMPK activator according to the present invention is used to treat metabolic disorders including diabetes, obesity, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), liver fibrosis, and dyslipidemia; cardiovascular diseases including atherosclerosis, hypertension, heart failure, and ischemic heart disease; neurodegenerative diseases including Alzheimer's disease and Parkinson's disease; inflammatory bowel disease; and rheumatoid arthritis. It can be used to prevent, treat, or improve one or more of the following conditions selected from inflammatory diseases including arthritis, leukemia, and cancer, but is not limited to these. In one exemplary implementation, the AMPK activator can also be used as a hypoglycemic agent, a cholesterol-lowering agent, or a fatty acid-lowering agent. 【0074】 In the AMPK activator according to the present invention, the AMPK activator can be used in the manufacture of compositions for anti-aging or life extension. 【0075】 The AMPK activator according to the present invention can be used in the manufacture of compositions for enhancing immunity, improving physical strength, improving physical endurance, increasing energy levels, increasing vitality, enhancing physical recovery, or supporting sustained physical activity. 【0076】 In the AMPK activator according to the present invention, the AMPK activator can also be used as an agent for promoting (stem) cell differentiation and maturation. 【0077】 In the AMPK activator according to the present invention, the concentration of 1,1-diethoxyethane can be 1 mM to 25 mM. 【0078】 2. Compositions for increasing insulin sensitivity or improving insulin resistance The present invention The present invention aims to provide a composition for increasing insulin sensitivity or improving insulin resistance, comprising 1,1-diethoxyethane (1,1-DEE) as an active ingredient. 【0079】 In the insulin sensitivity increasing or resistance improving composition according to the present invention, the 1,1-diethoxyethane can induce oxidative inactivation of PTEN through the formation of a disulfide bond between the Cys124 and Cys71 residues of PTEN. 【0080】 In the insulin sensitivity increasing or resistance improving composition according to the present invention, the 1,1-diethoxyethane can activate Akt by increasing phosphorylation at Ser473 and Thr308 of Akt. 【0081】 In the insulin sensitivity increasing or resistance improving composition according to the present invention, the 1,1-diethoxyethane can promote glycolysis by increasing phosphorylation at the Ser483 residue of PFKFB2 (6-phosphofructo-2-kinase / fructose-2,6-biphosphatase 2). 【0082】 In the insulin sensitivity increasing or resistance improving composition according to the present invention, the 1,1-diethoxyethane can be used for the prevention, treatment, or improvement of diseases related to insulin resistance. The insulin sensitivity increasing or resistance improving composition may include one or more selected from metabolic disorders, impaired blood glucose regulation, prevention and reversal of diabetes progression, diabetic complications, impaired weight management, protection and improvement of pancreatic beta cells, liver disease, and insulin-related disorders. 【0083】 In one example, the metabolic disorder may include, but is not limited to, type 1 diabetes, type 2 diabetes, impaired glucose tolerance (IGT), impaired fasting glucose (IFG), hyperglycemia, postprandial hyperglycemia, polycystic ovary syndrome (PCOS), hyperlipidemia, hypertension, overweight, obesity, and metabolic syndrome. 【0084】 In one example, the impaired blood glucose regulation may include, but is not limited to, a decrease in fasting plasma glucose (FPG), postprandial plasma glucose (PPG), and / or glycated hemoglobin (HbA1c), and improved blood glucose control. 【0085】 In one realization, the diabetes progression-related impairment may include, but is not limited to, the prevention, slowing, delaying, or reversal of the progression from impaired glucose tolerance (IGT), impaired fasting blood glucose (IFG), insulin resistance, or metabolic syndrome to type 2 diabetes. 【0086】 In one example, the aforementioned diabetic complications may include, but are not limited to, cataracts, microvascular and macrovascular diseases, nephropathy, retinopathy, neuropathy, tissue ischemia, diabetic foot disease, atherosclerosis, myocardial infarction, acute coronary syndrome, unstable angina, stable angina, stroke, peripheral artery occlusive disease, cardiomyopathy, heart failure, cardiac arrhythmia, and vascular restenosis. 【0087】 In one implementation example, the weight management disorder may include, but is not limited to, weight loss, prevention of weight gain, or promotion of weight loss. 【0088】 In one implementation example, the pancreatic beta-cell related disorder may include, but is not limited to, the prevention, slowing, delaying, or treatment of pancreatic beta-cell degeneration and / or pancreatic beta-cell dysfunction, the improvement and / or restoration of pancreatic beta-cell function, and / or the restoration of pancreatic insulin secretion function. 【0089】 In one example, the liver-related disease may include, but is not limited to, the prevention, slowing, delaying, or treatment of a disease or condition caused by abnormal accumulation of liver fat. 【0090】 In one implementation example, the insulin-related disorder may include, but is not limited to, maintaining and / or improving insulin sensitivity, or preventing or treating hyperinsulinemia and / or insulin resistance. 【0091】 3. Compositions for the prevention, improvement, or treatment of obesity or related metabolic diseases The present invention The present invention aims to provide a composition for the prevention, improvement, or treatment of obesity or related metabolic diseases, comprising 1,1-diethoxyethane (1,1-DEE) as an active ingredient. 【0092】 In the composition for the prevention, improvement, or treatment of obesity or related metabolic diseases according to the present invention, the obesity-related metabolic diseases may include, but are not limited to, type 2 diabetes, fatty liver, hyperlipidemia, hypertension, insulin resistance, arteriosclerosis, stroke, polycystic ovary syndrome (PCOS), metabolic syndromes, inflammatory bowel disease (IBD), and sleep apnea. 【0093】 4.Applications The present invention aims to provide a pharmaceutical composition, cosmetic composition, food composition, or animal feed composition using 1,1-diethoxyethane (1,1-DEE) as an active ingredient. 【0094】 (1) Pharmaceutical composition According to one example, The present invention aims to provide a pharmaceutical composition containing 1,1-diethoxyethane (1,1-DEE) as an active ingredient for the prevention or treatment of diseases requiring AMPK (AMP-activated protein kinase) activation, as well as for anti-aging, life extension, or enhancement of physical vitality. 【0095】 In the pharmaceutical composition according to the present invention, the disease requiring AMPK activation may include, but is not limited to, one or more of the following: metabolic disorders including diabetes, obesity, nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), liver fibrosis, and dyslipidemia; cardiovascular diseases including atherosclerosis, hypertension, heart failure, and ischemic heart disease; neurodegenerative diseases including Alzheimer's disease and Parkinson's disease; inflammatory diseases including inflammatory bowel disease and rheumatoid arthritis; leukemia; and cancer. 【0096】 In the pharmaceutical composition according to the present invention, the enhancement of physical vitality may include, but is not limited to, one or more selected from the following: enhancement of immunity, improvement of physical strength, improvement of physical endurance, increase of energy levels, increase of vitality, enhancement of physical recovery ability, or support for sustained physical activity. 【0097】 According to other implementation examples, The present invention aims to provide a pharmaceutical composition for the prevention or treatment of diseases related to insulin resistance, comprising 1,1-diethoxyethane (1,1-DEE) as an active ingredient. 【0098】 In the pharmaceutical composition according to the present invention, the diseases related to insulin resistance include type 1 diabetes, type 2 diabetes, impaired glucose tolerance (IGT), impaired fasting glucose (IFG), hyperglycemia, postprandial hyperglycemia, polycystic ovary syndrome (PCOS), hyperlipidemia, hypertension, overweight, obesity, and metabolic syndromes; fasting plasma glucose (FPG), postprandial plasma glucose Glucose dysregulation, including a decrease in glucose (PPG) and / or glycated hemoglobin (HbA1c) and improved blood glucose control; diabetes progression-related disorders, including prevention, slowing, delaying, or reversal of progression from impaired glucose tolerance (IGT), impaired fasting glucose (IFG), insulin resistance, or metabolic syndrome to type 2 diabetes;Diabetic complications including cataracts, microvascular and macrovascular diseases, nephropathy, retinopathy, neuropathy, tissue ischemia, diabetic foot disease, atherosclerosis, myocardial infarction, acute coronary syndrome, unstable angina, stable angina, stroke, peripheral artery occlusive disease, cardiomyopathy, heart failure, cardiac arrhythmia, and vascular restenosis; weight loss, prevention of weight gain, or promotion of weight loss. This may include, but is not limited to, one or more of the following: weight management disorders including weight loss; pancreatic beta-cell related disorders including prevention, slowing, delaying, or treating pancreatic beta-cell degeneration and / or beta-cell dysfunction, improvement and / or restoration of pancreatic beta-cell function, and / or restoration of pancreatic insulin secretion function; liver diseases including prevention, slowing, delaying, or treating disease or condition due to abnormal accumulation of liver fat; and insulin-related disorders including maintenance and / or improvement of insulin sensitivity, and prevention or treatment of hyperinsulinemia and / or insulin resistance. 【0099】 Furthermore, according to other implementation examples, The present invention aims to provide a pharmaceutical composition for the prevention or treatment of obesity or related metabolic diseases, comprising 1,1-diethoxyethane as an active ingredient. 【0100】 In the pharmaceutical composition according to the present invention, the obesity-related metabolic disease may include, but is not limited to, type 2 diabetes, fatty liver, hyperlipidemia, hypertension, insulin resistance, arteriosclerosis, stroke, polycystic ovary syndrome (PCOS), metabolic syndrome, inflammatory bowel disease (IBD), and sleep apnea. 【0101】 In the pharmaceutical composition according to the present invention, the pharmaceutical composition can be administered by oral administration, intravenous injection, subcutaneous injection, intramuscular injection, intraperitoneal injection, epithelial administration, local administration, vaginal administration, pulmonary administration, rectal administration, sublingual administration, buccal administration, transdermal administration, ocular administration, inhalation, intracavernosal injection, intrathecal injection, epidural injection, and rectal administration. When administered orally, for example, the pharmaceutical composition can be formulated as an uncoated tablet or by coating the active agent or protecting it from degradation in the stomach. The composition may also be administered by any device that allows the active substance to move to target cells. The route of administration can vary depending on the general conditions and age of the patient being treated, the nature of the treatment condition, and the selected active ingredient. 【0102】 In the pharmaceutical composition according to the present invention, the pharmaceutical composition may be supported on a carrier, and the carrier may include, but is not limited to, one or more selected from viral particles, vesicles, nanoparticles, microparticles, liposomes, transposons, micelles, antibodies, and exosomes. 【0103】 In the pharmaceutical composition according to the present invention, the appropriate dosage of the pharmaceutical composition varies depending on factors such as the formulation method, administration method, patient's age, weight, sex, condition, diet, administration time, route of administration, excretion rate, and response sensitivity. A skilled physician can usually easily determine and prescribe a dosage effective for the desired treatment or prevention. For example, the pharmaceutical composition can be administered in a single or multiple dose, divided into one to four doses per day. For instance, the pharmaceutical composition may contain 0.01 mg / kg to 100 mg / kg per adult, preferably 0.02 mg / kg to 90 mg / kg, and more preferably 0.03 mg / kg to 80 mg / kg. 【0104】 In the pharmaceutical composition according to the present invention, the pharmaceutical composition may be manufactured in unit volume form or by being contained in a multi-volume container by formulating with pharmaceutically acceptable carriers and / or excipients in a manner readily available to a person with ordinary skill in the art to which the invention pertains. In this case, the dosage form may be in the form of a solution, suspension or emulsion in an oil or aqueous medium, or in the form of an extract, powder, granules, tablet or capsule, and may contain additional dispersants or stabilizers. The pharmaceutical composition may also be administered in the form of a suppository, spray, ointment, cream, gel, inhalant or skin patch. Furthermore, the pharmaceutical composition may be manufactured for mammalian administration, more preferably for human administration. 【0105】 In the pharmaceutical composition according to the present invention, the pharmaceutically acceptable carrier may be a solid or a liquid, and may be one or more selected from excipients, antioxidants, buffers, bacteriostatic agents, dispersants, adsorbents, surfactants, binders, preservatives, disintegrants, sweeteners, flavoring agents, lubricants, release regulators, wetting agents, stabilizers, suspending agents, and lubricants. The pharmaceutically acceptable carrier may also be selected from saline solution, sterile water, Ringer's solution, buffered saline solution, dextrose solution, maltodextrin solution, glycerol, ethanol, and mixtures thereof. 【0106】 In one specific example, suitable fillers may include, but are not limited to, sugars (e.g., dextrose, sucrose, maltose, lactose), starch (e.g., corn starch), sugar alcohols (e.g., mannitol, sorbitol, maltitol, erythritol, and xylitol), starch hydrolysates (e.g., dextrin and maltodextrin), cellulose or cellulose derivatives (e.g., microcrystalline cellulose), or mixtures thereof. 【0107】 In one specific example, suitable binders may include, but are not limited to, povidone, copovidone, methylcellulose, hydroxymethylcellulose, hydroxypropylmethylcellulose, hydroxypropylcellulose, hydroxyethylcellulose, gelatin, gums, sucrose, starch, or mixtures thereof. 【0108】 In one specific example, suitable preservatives may include, but are not limited to, benzoic acid, sodium benzoate, benzyl alcohol, butylated hydroxyanisole, butylated hydroxytoluene, chlorobutol, gallate, hydroxybenzoic acid, EDTA, or mixtures thereof. 【0109】 In one specific example, suitable disintegrants may include, but are not limited to, sodium starch glycolate, cross-linked polyvinylpyrrolidone, cross-linked carboxymethylcellulose, starch, microcrystalline cellulose, or mixtures thereof. 【0110】 In one specific example, suitable sweeteners may include, but are not limited to, sucralose, saccharin, sodium or potassium, or calcium saccharin, acesulfame potassium or sodium cyclamate, mannitol, fructose, sucrose, maltose, or mixtures thereof. 【0111】 In one specific example, suitable glidants include, but are not limited to, silica, colloidal silicon dioxide, and talc. 【0112】 In one specific example, suitable lubricants may include, but are not limited to, long-chain fatty acids and their salts, such as magnesium stearate and stearic acid, talc, glyceride wax, or mixtures thereof. 【0113】 (2) Cosmetic composition The present invention aims to provide a cosmetic composition for the prevention or improvement of diseases requiring AMPK (AMP-activated protein kinase) activation, anti-aging, life extension, or enhancement of physical vitality, containing 1,1-diethoxyethane (1,1-DEE) as an active ingredient. 【0114】 In the cosmetic composition according to the present invention, the disease requiring AMPK activation may include, but is not limited to, one or more of the following: metabolic disorders including diabetes, obesity, nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), liver fibrosis, and dyslipidemia; cardiovascular diseases including atherosclerosis, hypertension, heart failure, and ischemic heart disease; neurodegenerative diseases including Alzheimer's disease and Parkinson's disease; inflammatory diseases including inflammatory bowel disease and rheumatoid arthritis; leukemia; and cancer. 【0115】 In the cosmetic composition according to the present invention, the enhancement of physical vitality may include, but is not limited to, one or more selected from the following: enhancement of immunity, improvement of physical strength, improvement of physical endurance, increase of energy levels, increase of vitality, enhancement of physical recovery ability, or support for sustained physical activity. 【0116】 In the cosmetic composition according to the present invention, the cosmetic composition can be used for skin regeneration, wrinkle improvement, or skin moisturizing. 【0117】 According to other implementation examples, The present invention aims to provide a cosmetic composition for the prevention or improvement of diseases related to insulin resistance, comprising 1,1-diethoxyethane (1,1-DEE) as an active ingredient. 【0118】 In the cosmetic composition according to the present invention, the diseases related to insulin resistance include metabolic disorders such as Type 1 diabetes, Type 2 diabetes, Impaired Glucose Tolerance (IGT), Impaired Fasting Glucose (IFG), Hyperglycemia, Postprandial Hyperglycemia, Polycystic Ovary Syndrome (PCOS), Hyperlipidemia, Hypertension, Overweight, Obesity, and Metabolic Syndrome; Fasting Plasma Glucose (FPG), Postprandial Plasma Glucose dysregulation, including a decrease in glucose (PPG) and / or glycated hemoglobin (HbA1c) and improved blood glucose control; diabetes progression-related disorders, including prevention, slowing, delaying, or reversal of progression from impaired glucose tolerance (IGT), impaired fasting glucose (IFG), insulin resistance, or metabolic syndrome to type 2 diabetes;Diabetic complications including cataracts, microvascular and macrovascular diseases, nephropathy, retinopathy, neuropathy, tissue ischemia, diabetic foot disease, atherosclerosis, myocardial infarction, acute coronary syndrome, unstable angina, stable angina, stroke, peripheral artery occlusive disease, cardiomyopathy, heart failure, cardiac arrhythmia, and vascular restenosis; weight loss, prevention of weight gain, or promotion of weight loss. This may include, but is not limited to, one or more of the following: weight management disorders including weight loss; pancreatic beta-cell related disorders including prevention, slowing, delaying, or treating pancreatic beta-cell degeneration and / or beta-cell dysfunction, improvement and / or restoration of pancreatic beta-cell function, and / or restoration of pancreatic insulin secretion function; liver diseases including prevention, slowing, delaying, or treating disease or condition due to abnormal accumulation of liver fat; and insulin-related disorders including maintenance and / or improvement of insulin sensitivity, and prevention or treatment of hyperinsulinemia and / or insulin resistance. 【0119】 Furthermore, according to other implementation examples, The present invention aims to provide a cosmetic composition for preventing or improving cellulite, containing 1,1-diethoxyethane (1,1-DEE) as an active ingredient. 【0120】 As used herein, the term "cellulite" refers to the appearance of unevenly protruding fat, particularly on the thighs or buttocks, due to circulatory problems caused by the accumulation of excess fat and waste products. The root cause of cellulite is fundamentally an increase or enlargement of fat cells. Therefore, the above-mentioned term "prevention or improvement of cellulite" may mean a reduction in the volume of cellulite, a decrease in the height of cellulite, the removal of cellulite, or a flattening of the cellulite and its surroundings. 【0121】 The 1,1-diethoxyethane (1,1-DEE) according to the present invention has the effect of suppressing fat accumulation and preventing or improving cellulite. Furthermore, due to these effects, the composition has a body slimming effect. The term "body slimming" may mean promoting the uniform redistribution of fat in body lines that are uneven due to uneven distribution of fat under the skin, reducing the volume of the body or a part of the body, eliminating swelling and consequently reducing the volume of a part of the body, improving localized obesity, breaking down and eliminating fat from fat cells, and reducing the accumulation of triglycerides and body fluids in fat cells. 【0122】 In the cosmetic composition according to the present invention, the cosmetic composition may further contain a dermatologically acceptable carrier. The dermatologically acceptable carrier may include, but is not limited to, purified water, oil, wax, fatty acid, fatty acid alcohol, fatty acid ester, surfactant, hygroscopic agent, thickener, antioxidant, viscosity stabilizer, chelating agent, buffer, preservative, lower alcohol, etc., and its type and concentration can vary and can be modified within the scope of the present invention by those skilled in the art. 【0123】 In the cosmetic composition according to the present invention, in addition to the active ingredient of the present invention, the cosmetic composition may optionally contain functional substances such as whitening agents, moisturizers, anti-inflammatory agents, antibacterial agents, antifungal agents, vitamins, ultraviolet blocking agents, antibiotics, acne inhibitors, perfumes, and dyes, which can be included in the cosmetic composition according to the present invention in amounts commonly used in the cosmetics field. In order to enhance its functional effect, the cosmetic composition of the present invention may further contain one or more moisturizing active ingredients having the same or equivalent function as the composition of the present invention. 【0124】 In the cosmetic composition according to the present invention, the cosmetic composition can be manufactured in the form of a general emulsifier and a solubilizer. Examples of cosmetics in the emulsifier form include nourishing lotions, creams, and essences, and examples of cosmetics in the solubilizer form include softening lotions. In addition to the active ingredient of the present invention, the cosmetic composition may be manufactured in the form of an auxiliary agent that can be applied topically or systemically and is commonly used in the industry, by containing a dermatologically acceptable medium or base. Suitable cosmetic dosage forms may include, for example, solutions, gels, solids or paste anhydrous products, emulsions obtained by dispersing an oil phase in an aqueous phase, suspensions, microemulsions, microcapsules, fine granules, or ionic (liposomes) or nonionic camphor dispersants, creams, lotions, powders, ointments, sprays, or conceal sticks. It can also be manufactured in the form of a foam or an aerosol composition further containing a compressed propellant. 【0125】 In the cosmetic composition according to the present invention, the cosmetic composition can be formulated into one or more of the following: a solution, an external ointment, a cream, a foam, a nourishing lotion, a softening lotion, a perfume, a pack, a softening water, an emulsion, a makeup base, an essence, a soap, a liquid cleanser, a bath additive, a sunscreen cream, a sun oil, a suspension, an emulsion, a paste, a gel, a lotion, a powder, a soap, a surfactant-containing cleanser, an oil, a powder foundation, an emulsion foundation, a wax foundation, a patch, and a spray. 【0126】 (3) Food composition As used herein, the term "food" means a natural product or processed product containing one or more nutrients, preferably one that has undergone some processing steps and is ready to be eaten directly, and can generally include all foods, food additives, functional foods and beverages. 【0127】 As used herein, the terms "functional food" or "health functional food" refer to a group of foods to which added value has been added using physical, biochemical, or biotechnological methods to act on and express the functions of the food in question for a specific purpose, or foods that have been designed and processed to fully express in the body the internal regulatory functions related to the regulation of biological defense rhythms, disease prevention and recovery, etc. Specifically, these may be health functional foods. The above functional foods may contain food-grade acceptable food additives and may further contain appropriate carriers, excipients, and diluents commonly used in the manufacture of functional foods. The types of the above health supplements are not limited to these, but may be in the form of powder, granules, tablets, capsules, or beverages. 【0128】 According to one example, The present invention aims to provide a food composition containing 1,1-diethoxyethane (1,1-DEE) as an active ingredient for the prevention or improvement of diseases requiring AMPK (AMP-activated protein kinase) activation, as well as for anti-aging or life extension. 【0129】 In the food composition according to the present invention, the diseases requiring AMPK activation may include, but are not limited to, one or more of the following: metabolic disorders including diabetes, obesity, nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), liver fibrosis, and dyslipidemia; cardiovascular diseases including atherosclerosis, hypertension, heart failure, and ischemic heart disease; neurodegenerative diseases including Alzheimer's disease and Parkinson's disease; inflammatory diseases including inflammatory bowel disease and rheumatoid arthritis; leukemia; and cancer. 【0130】 In the food composition according to the present invention, the enhancement of physical vitality may include, but is not limited to, one or more selected from the following: enhancement of immunity, improvement of physical strength, improvement of physical endurance, increase of energy levels, increase of vitality, enhancement of physical recovery ability, or support for sustained physical activity. 【0131】 According to other implementation examples, The present invention aims to provide a food composition for the prevention or improvement of diseases related to insulin resistance, comprising 1,1-diethoxyethane (1,1-DEE) as an active ingredient. 【0132】 In the food composition according to the present invention, the diseases related to insulin resistance include type 1 diabetes, type 2 diabetes, impaired glucose tolerance (IGT), impaired fasting glucose (IFG), hyperglycemia, postprandial hyperglycemia, polycystic ovary syndrome (PCOS), hyperlipidemia, hypertension, overweight, obesity, and metabolic syndrome; fasting plasma glucose (FPG), postprandial plasma glucose Glucose dysregulation, including a decrease in glucose (PPG) and / or glycated hemoglobin (HbA1c) and improved blood glucose control; diabetes progression-related disorders, including prevention, slowing, delaying, or reversal of progression from impaired glucose tolerance (IGT), impaired fasting glucose (IFG), insulin resistance, or metabolic syndrome to type 2 diabetes;Diabetic complications including cataracts, microvascular and macrovascular diseases, nephropathy, retinopathy, neuropathy, tissue ischemia, diabetic foot disease, atherosclerosis, myocardial infarction, acute coronary syndrome, unstable angina, stable angina, stroke, peripheral artery occlusive disease, cardiomyopathy, heart failure, cardiac arrhythmia, and vascular restenosis; weight loss, prevention of weight gain, or promotion of weight loss. This may include, but is not limited to, one or more of the following: weight management disorders including weight loss; pancreatic beta-cell related disorders including prevention, slowing, delaying, or treating pancreatic beta-cell degeneration and / or beta-cell dysfunction, improvement and / or restoration of pancreatic beta-cell function, and / or restoration of pancreatic insulin secretion function; liver diseases including prevention, slowing, delaying, or treating disease or condition due to abnormal accumulation of liver fat; and insulin-related disorders including maintenance and / or improvement of insulin sensitivity, and prevention or treatment of hyperinsulinemia and / or insulin resistance. 【0133】 Furthermore, according to other implementation examples, The present invention aims to provide a food composition for preventing or improving obesity or related metabolic diseases, comprising 1,1-diethoxyethane (1,1-DEE) as an active ingredient. 【0134】 In the food composition according to the present invention, the obesity-related metabolic disease may include, but is not limited to, type 2 diabetes, fatty liver, hyperlipidemia, hypertension, insulin resistance, arteriosclerosis, stroke, polycystic ovary syndrome (PCOS), metabolic syndrome, inflammatory bowel disease (IBD), and sleep apnea. 【0135】 The food composition according to the present invention is characterized in that the food is meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gum, dairy products including ice cream, various soups, drinking water, tea, coffee beverages, energy drinks, alcoholic beverages, or vitamin complexes. 【0136】 In the food composition according to the present invention, the food composition may contain various nutrients, vitamins, electrolytes, flavoring agents, coloring agents, pectinic acid and its salts, alginic acid and its salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, carbonation agents used in carbonated beverages, and the like. In addition, the composition of the present invention may contain fruit pulp for the production of natural fruit juice, fruit juice beverages, or vegetable beverages. These components can be used independently or in combination. 【0137】 In the food composition according to the present invention, the term "functional food" or "health functional food" means a group of foods to which added value has been added using physical, biochemical, or biotechnological methods to act and express the functions of the food in question for a specific purpose, or a food composition that has been designed and processed to fully express in the body the internal regulatory functions related to the regulation of biological defense rhythms, disease prevention and recovery, etc. Specifically, it can be a health functional food. The functional food may contain food-grade acceptable food additives and may further contain appropriate carriers, excipients, and diluents that are commonly used in the manufacture of functional foods. 【0138】 (4) Feed composition According to one example, The present invention aims to provide a feed composition containing 1,1-diethoxyethane (1,1-DEE) as an active ingredient for the prevention or improvement of diseases requiring AMPK (AMP-activated protein kinase) activation, as well as for anti-aging, life extension, or enhancement of physical vitality. 【0139】 In the feed composition according to the present invention, the diseases requiring AMPK activation may include, but are not limited to, one or more selected from metabolic disorders including diabetes, obesity, nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), liver fibrosis, and dyslipidemia; cardiovascular diseases including atherosclerosis, hypertension, heart failure, and ischemic heart disease; neurodegenerative diseases including Alzheimer's disease and Parkinson's disease; inflammatory diseases including inflammatory bowel disease and rheumatoid arthritis; leukemia; and cancer. 【0140】 In the feed composition according to the present invention, the enhancement of physical vitality may include, but is not limited to, one or more selected from the following: enhancement of immunity, improvement of physical strength, improvement of physical endurance, increase in energy levels, increase in vitality, enhancement of physical recovery ability, or support for sustained physical activity. 【0141】 According to other implementation examples, The present invention aims to provide a feed composition for the prevention or improvement of insulin resistance-related diseases, comprising 1,1-diethoxyethane (1,1-DEE) as an active ingredient. 【0142】 In the feed composition according to the present invention, the diseases related to insulin resistance include type 1 diabetes, type 2 diabetes, impaired glucose tolerance (IGT), impaired fasting glucose (IFG), hyperglycemia, postprandial hyperglycemia, polycystic ovary syndrome (PCOS), hyperlipidemia, hypertension, overweight, obesity, and metabolic syndrome; fasting plasma glucose (FPG), postprandial plasma glucose Glucose dysregulation, including a decrease in glucose (PPG) and / or glycated hemoglobin (HbA1c) and improved blood glucose control; diabetes progression-related disorders, including prevention, slowing, delaying, or reversal of progression from impaired glucose tolerance (IGT), impaired fasting glucose (IFG), insulin resistance, or metabolic syndrome to type 2 diabetes;Diabetic complications including cataracts, microvascular and macrovascular diseases, nephropathy, retinopathy, neuropathy, tissue ischemia, diabetic foot disease, atherosclerosis, myocardial infarction, acute coronary syndrome, unstable angina, stable angina, stroke, peripheral artery occlusive disease, cardiomyopathy, heart failure, cardiac arrhythmia, and vascular restenosis; weight loss, prevention of weight gain, or promotion of weight loss. This may include, but is not limited to, one or more of the following: weight management disorders including weight loss; pancreatic beta-cell related disorders including prevention, slowing, delaying, or treating pancreatic beta-cell degeneration and / or beta-cell dysfunction, improvement and / or restoration of pancreatic beta-cell function, and / or restoration of pancreatic insulin secretion function; liver diseases including prevention, slowing, delaying, or treating disease or condition due to abnormal accumulation of liver fat; and insulin-related disorders including maintenance and / or improvement of insulin sensitivity, and prevention or treatment of hyperinsulinemia and / or insulin resistance. 【0143】 In the feed composition according to the present invention, the insulin resistance-related disease may include, but is not limited to, one or more selected from insulin resistance syndrome, hypertension, arteriosclerosis, dyslipidemia, fatty liver, hyperinsulinemia, myocardial infarction, stroke, heart failure, arrhythmia, cataract, diabetic complications, or diabetes. 【0144】 Furthermore, according to other implementation examples, The present invention aims to provide a feed composition for the prevention or improvement of obesity or related metabolic diseases, comprising 1,1-diethoxyethane (1,1-DEE) as an active ingredient. 【0145】 In the feed composition according to the present invention, the obesity-related metabolic disease may include, but is not limited to, type 2 diabetes, fatty liver, hyperlipidemia, hypertension, insulin resistance, arteriosclerosis, stroke, polycystic ovary syndrome (PCOS), metabolic syndrome, inflammatory bowel disease (IBD), and sleep apnea. 【0146】 In the feed composition according to the present invention, the feed contains nutrients necessary for animals, such as energy, protein, lipids, vitamins, and minerals, and may be, but is not limited to, plant-based feed such as grains, root fruits, food processing by-products, algae, fiber, oils and fats, starches, gourds, and grain by-products, or animal-based feed such as proteins, inorganic substances, milk fats, mineral substances, oils and fats, and single-cell proteins. 【0147】 In the feed composition according to the present invention, the feed includes, but is not limited to, powdered feed, solid feed, moist pellet feed, dry pellet feed, EP (Extruder Pellet) feed, and live feed. 【0148】 In the feed composition according to the present invention, the feed composition may include binders, emulsifiers, and preservatives added to prevent deterioration of quality, and the feed composition may also include feed additives. Examples of additives to the feed to increase efficacy include amino acids, vitamins, enzymes, flavoring agents, non-protein nitrogen compounds, silicates, buffers, extractants, and oligosaccharides. Other materials such as feed mixtures may also be included, but are not limited to these. 【0149】 5.Treatment method According to one example, The present invention aims to provide a method for preventing or treating a disease requiring AMPK activation, comprising the step of administering to an individual an AMPK activator according to item 1 or a pharmaceutical composition according to item 2(1) containing the AMPK activator as an active ingredient. 【0150】 According to other implementation examples, The present invention aims to provide a method for preventing or treating a disease related to insulin resistance, comprising the step of administering to an individual a composition for increasing insulin sensitivity or improving insulin resistance according to item 2 above, or a pharmaceutical composition according to item 2(1) containing 1,1-diethoxyethane (1,1-DEE) as an active ingredient. 【0151】 Furthermore, according to other implementation examples, The present invention aims to provide a method for preventing or treating obesity or related metabolic diseases, comprising the step of administering to an individual a composition for preventing, improving, or improving obesity or related metabolic diseases, which contains the aforementioned 1,1-diethoxyethane (1,1-DEE) as an active ingredient. 【0152】 In the method according to the present invention, the obesity-related metabolic disease may include, but is not limited to, type 2 diabetes, fatty liver, hyperlipidemia, hypertension, insulin resistance, arteriosclerosis, stroke, polycystic ovary syndrome (PCOS), metabolic syndrome, inflammatory bowel disease (IBD), and sleep apnea. 【0153】 In the method according to the present invention, the individual mentioned above includes, but is not limited to, humans, cattle, monkeys, horses, sheep, pigs, chickens, turkeys, quail, cats, dogs, mice, rats, rabbits, or guinea pigs. 【0154】 In the method according to the present invention, the administration route, dosage, and frequency of administration of the pharmaceutical composition can be varied depending on the patient's condition and the presence or absence of side effects, and the optimal administration method, dosage, and frequency can be selected within an appropriate range by a skilled technician. In the present invention, a suitable dosage of the exosome or pharmaceutical composition may range from 0.001 mg / kg to 100 mg / kg per adult per day, depending on the patient's condition, weight, sex, age, severity of the patient's condition, and administration route. Administration may be once a day or in several divided doses. These dosages should not be construed as limiting the scope of the present invention in any way. 【0155】 The following examples present various embodiments to aid in understanding the invention. These embodiments are provided to make the invention easier to understand, and the scope of protection of the invention is not limited by these embodiments. 【0156】 I. AMPK activator <Materials and Methods> 1.Material 1,1-DEE (A902), 2',7'-dichlorofluorescein diacetate (DCFH-DA) (#35845), N-acetyl-L-cysteine ​​(A9165), and hydrogen peroxide (H2O2, #88579) were purchased from Sigma-Aldrich (St. Louis, MO, USA). 1,2-DEE was purchased from Tokyo Chemical Industry (Tokyo, Japan). The EZ-Cytox assay kit (EZ-3000) was purchased from DoGenBio (Geumcheon, Seoul, Republic of Korea). MitoTracker® Red CMXRos (#9082) and protease / phosphatase inhibitor cocktail (100x, #5872) were purchased from Cell Signaling Technology (CST, Danvers, MA, USA). 【0157】 The following antibodies were used: AMPK (#2532, 1:1000), phosphorylated AMPK (Thr172) (#2535, 1:1000), ACC (#3676, 1:1000), phosphorylated ACC (Ser79) (#11818, 1:1000), PFKFB2 (#13029, 1:1000), phosphorylated PFKFB2 (Ser483) (#13064, 1:1000), PGC-1α (#2178, 1:1000), Nrf1 (nuclear respiratory factor 1) (#46743, 1:1000), Nrf2 (#12721, 1:1000), and β-actin (#4970, 1:1000) antibody (CST). Additionally, PGC-1α (#PA5-72948, 1:1000) and mitochondrial transcription factor A (Tfam) (#MA5-16148, 1:1000) antibodies were purchased from Invitrogen. GAPDH (LF-PA0212, 1:1000) and anti-rabbit IgG horseradish peroxidase conjugated (LF-SA8002, 1:5000) antibodies were purchased from AbFrontier (Daejeon, Korea). 【0158】 2. Cell culture and processing AC16 cells were maintained in Dulbecco's modified Eagle medium / nutrient mixture F-12 (DMEM / F12, LM002-05) supplemented with FBS (fetal bovine serum, S001-01) and 1× penicillin / streptomycin (P / S, LS 202-02) (Welgene, Gyeongsan, Korea). Cells were trypsinized with 1× trypsin-EDTA (#25300-062) at 70% density and subcultured. For specific experiments, cells were seeded into 6-well plates and allowed to adhere overnight. 1,1-DEE was diluted in serum-free medium before culturing with cells. 【0159】 Wild-type (WT) and AMPKα double knockout (DKO) mouse embryonic fibroblast (MEF) cell lines were provided by the College of Medicine, Chia Chuan University, and cultured in DMEM (LM001-05) supplemented with 10% (v / v) FBS and 1×P / S (Welgene). 【0160】 3. Survival Rate Assay The cytotoxicity of 1,1-DEE was evaluated using the EZ-Cytox assay according to the manufacturer's protocol. Cells were inoculated into 96-well plates (17,000 cells / 10 μL / well) and incubated overnight in an incubator (37°C, 5% CO2). The following day, cells were cultured with 1,1-DEE for 24 hours. After 24 hours of culture, cells were treated with EZ-Cytox reagent (1:10 v / v) and cultured for 30 minutes. The signal was detected at 450 nm using a microplate reader. Cell viability was calculated using Equation 1 below, and the results were analyzed using GraphPad Prism 8.0.1 (San Diego, CA, USA). 【0161】 【number】 【0162】 In Equation 1 above, "blank" represents the absorbance of wells containing cell-free medium and EZ-Cytox, "control" represents the absorbance of wells containing cells and EZ-Cytox but untreated with 1,1-DEE, and "exp" represents the absorbance of wells containing cells, 1,1-DEE, and EZ-Cytox. 【0163】 4. Assessment of mitochondrial oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) Mitochondrial oxygen (OCR) and extracellular acidification rate (ECAR) were evaluated using the Agilent Seahorse Mito Stress Test Kit (#103015-100, Seahorse Bioscience, Houston, TX, USA) according to the manufacturer's protocol. Prior to the assay, AC16 cells were placed in 1.8 × 10⁶ wells of a 96-well Seahorse cell culture microplate. 4 Cells were inoculated at a rate of cells / well and allowed to adhere overnight. The sensor cartridge was inserted into 200 μL of Seahorse XF calibration solution (#100840-000), hydrated, and cultured overnight at 37°C in a CO2-free incubator. Following the modified protocol, cells were washed on the day of assay and replaced with 180 μL / well containing Seahorse XF DMEM (#103575-100). OCR and ECAR were evaluated using a Seahorse Xfe96 analyzer (Agilent, California, USA) by sequentially injecting 1,1-DEE, oligomycin (1.5 μM), carbonyl cyanide-4 (trifluoromethoxy)phenylhydrazone (FCCP) (1.5 μM), and rotenone / antimycin (0.5 μM) into the injection port. Results were analyzed using GraphPad Prism 8.0.1. 【0164】 5. Immunofluorescence staining and flow cytometry analysis Cells were seeded into 6-well plates and allowed to adhere overnight at 37°C under 5% CO2. The cells were then exposed to 1,1-DEE. For immunofluorescence staining, cells were washed with PBS after specific treatment and cultured at 37°C for 30 minutes under 5% CO2 in 10 μM DCFH-DA for ROS detection or in 200 nM MitoTracker® Red CMXRos for mitochondrial labeling. After culture, cells were washed twice with PBS. Images were acquired using a fluorescence microscope. For flow cytometry, cells were cultured with DCFH-DA or MitoTracker, collected after treatment with trypsin, and then fixed with 70% ethanol at 4°C for 30 minutes. DCFH-DA signals were detected using FACS Canto II at excitation and emission wavelengths of 485 and 535 nm, respectively, while MitoTracker Red signals were detected at excitation and emission wavelengths of 579 and 599 nm, respectively. 【0165】 6.Western blot analysis Cells were washed twice with Dulbecco phosphate-buffered saline (DPBS, LM001-01, Welgene), and then cell lysates were obtained using a lysis buffer containing 20 mM Tris-HCl (pH 7.5), 150 mM NaCl, 5% glycerol, 0.1% NP-40, and 1× protease / phosphatase inhibitor. The cell lysates were placed on ice and shaken every 5 minutes for 30 minutes. Cell debris was removed by centrifugation at 13,000 rpm for 10 minutes. The supernatant was then collected, and the protein concentration was measured using a BCA protein analysis kit (Pierce, USA). The lysates were mixed with a sample buffer containing 60 mM Tris (pH 6.8), 25% glycerol, 2% SDS, 5% 2-mercaptoethanol, 0.5% bromophenol, and 2-mercaptoethanol, and then heated at 95°C for 5 minutes. Next, the samples were applied to SDS-PAGE and transferred by electrophoresis using an Immobilon PVDF membrane. The membranes were added to TBST containing 3% BSA and blocked at room temperature for 1 hour, followed by immunoblotting overnight with the primary antibody at 4°C. The following day, the membranes were washed three times with TBST and then cultured for an additional 1 hour with the equivalent secondary antibody. Finally, protein expression was detected using Immobilon chemiluminescent HRP substrate (#P90720, Merck Millipore) and Fusion Solo Vilber Lourmat (Vilber GmbH, Eberhardzell, Germany). Proteins were quantified using ImageJ software (ImageJ 1.5i, National Institutes of Health, Bethesda, MD, USA). 【0166】 7. RNA extraction, semi-quantitative PCR, and quantitative real-time PCR (qRT-PCR) Total RNA was extracted using Trizol reagent (#155960626, Ambion, Carlsbad, California, USA). RNA concentration was measured using a NanoDrop spectrophotometer, and purity was indicated by an A260 / A280 ratio of 1.8–2.0. Complementary DNA (cDNA) was extracted using Improm-II according to the manufacturer's protocol. TMThe cDNA was synthesized using reverse transcriptase (A3802, Promega, Madison, USA). The cDNA product was then subjected to semi-quantitative PCR using AccuPower® PCR Premix (Bioneer, Daejeon, Korea). Additionally, qRT-PCR was performed using TOPreal. TM The assay was performed using SYBR Green qPCR Premix (#RT500S, Enzynomics, Daejeon, Korea). The primers were purchased from Bioneer and are shown in Table 1 below. 【0167】 [Table 1] 【0168】 8.Statistical analysis Statistical analysis was performed using GraphPad Prism 8.0.1. Data were expressed as mean ± standard error of the mean (SEM). Statistical significance was analyzed using two-way ANOVA, and a p-value ≤ 0.05 was considered statistically significant. 【0169】 <Result> 1. Does 1,1-DEE transiently inhibit OCR and ECAR in AC16 cells? To evaluate the effect of 1,1-DEE (Figure 1A) on cell viability and determine the concentration to be used in experiments, EZ-Cytox analysis was performed. After treating cells with various concentrations of 1,1-DEE for 24 hours, cell viability was evaluated by adding EZ-Cytox reagent. No cytotoxicity was observed at concentrations below 25 mM (Figure 1B). Metformin treatment at the same concentration was also shown to be safe, and therefore 25 mM was selected as the maximum treatment concentration for subsequent experiments. 【0170】 Mitochondrial respiration was evaluated using the Agilent Seahorse XF96 Cell Mito Stress Test Kit. Cells were acutely infused with various concentrations of 1,1-DEE for 30 minutes, and mitochondrial respiration (OCR) and elevated mitochondrial respiration (ECAR) were monitored after sequential infusion of oligomycin, FCCP, and rotenone / antimycin as mitochondrial modulators. The results showed a sharp decrease in basal OCR immediately after 1,1-DEE infusion, followed by a reversible and rapid recovery. The decrease in OCR occurred at concentrations of 10–20 mM, but OCR did not fully recover after 30 minutes in this concentration range. In contrast, infusion of 1,2-DEE did not result in a significant change in OCR, and treatment with metformin at concentrations of 5–20 mM showed a gradual decrease in OCR after 30 minutes (Figure 1C). Furthermore, mitochondrial ATP-binding respiration, maximal respiration, and excess respiratory volume were evaluated through the infusion of oligomycin, FCCP, and rotenone / antimycin. Acute infusion of 1,1-DEE reduced ATP-bound respiration, maximal respiration, and excess respiratory volume at concentrations of 10–20 mM, but did not significantly alter proton leakage (Figure 1D). 【0171】 ECAR is measured by the amount of lactate converted from pyruvate excreted per minute and reflects the rate of glycolysis in cells. Acute infusion of 1,1-DEE resulted in a reversible decrease in ECAR, similar to basal OCR (Figure 1E), but treatment with 1,2-DEE and metformin did not result in any significant change in ECAR (Figure 1E). 【0172】 Overall, these results suggest that 1,1-DEE can rapidly modulate mitochondrial and glycolytic function, inducing a reversible decrease in mitochondrial oxidative phosphorylation (OXPHOS) and cellular glycolysis. 【0173】 2.1,1-DEE activates AMPK or not Eukaryotes possess a highly conserved homeostatic system to respond to a decrease in ATP levels when oxidative phosphorylation (OXPHOS) and glycolysis are reduced by mitochondrial toxins. A key component of this system is AMPK (AMP-activated protein kinase), the major regulator of cellular energy. AMPK is fully activated within minutes of OXPHOS suppression, playing a role in enhancing catabolism and weakening anabolism. 【0174】 To determine whether 1,1-DEE affects AMPK activation by phosphorylating the AMPK Ser172 residue via OXPHOS inhibition, AC16 cells were treated with various concentrations of 1,1-DEE for 10 minutes, and phosphorylated AMPK expression was analyzed. The results showed that phosphorylated AMPK expression increased 10 minutes after 1,1-DEE treatment (Figure 2A). 【0175】 Furthermore, cells were exposed to 1,1-DEE according to defined time intervals to confirm whether 1,1-DEE transiently induces AMPK activation. Acute exposure to 1,1-DEE confirmed that AMPK could be reversibly activated, as phosphorylated AMPK expression transiently increased and then decreased at 5 and 10 minutes (Figure 2B). On the other hand, 1,2-DEE exposure showed no difference in AMPK activation for 30 minutes (Figure 2C), and metformin treatment showed a gradual increase in AMPK phosphorylation after 60 minutes (Figure 2D). 【0176】 3. Elucidation of the regulatory mechanisms of fatty acid oxidation and glycolysis by 1,1-DEE-induced AMPK activation. AMPK regulates fatty acid metabolism through ACC (acetyl-CoA carboxylase) phosphorylation. When AMPK phosphorylates ACC, ACC activation is inhibited, and its synthesis is suppressed. When ACC is phosphorylated by AMPK, ACC activation is suppressed, and the production of malonyl-CoA, a substrate for fatty acid synthase (FAS), is reduced. Malonyl-CoA inhibits fatty acid β-oxidation in mitochondria, thereby allowing AMPK to regulate fatty acid oxidation. 【0177】 After treating AC16 cells with various concentrations of 1,1-DEE for 30 minutes, the phosphorylation levels of ACC and PFKFB2, downstream target proteins of AMPK, were analyzed. 1,1-DEE-activated AMPK phosphorylated the Ser79 residue of ACC, inhibiting ACC activity and promoting mitochondrial fatty acid β-oxidation by reducing fatty acid synthesis (Figure 3A). Furthermore, 1,1-DEE treatment was followed by a decrease in sterol regulatory element-binding protein-1c (SREBP-1c) and FASN gene expression, confirming that ACC activity could be suppressed (Figure 3B). AMPK is also known to regulate glycolysis through increased PFKFB2 activation; after 1,1-DEE exposure, increased phosphorylation at Ser466 and Ser483 residues of PFKFB2 was observed, leading to increased PFKFB2 activation and glycolysis (Figure 3A). 【0178】 To confirm whether ACC and PFKFB2 phosphorylation is regulated by AMPK, wild-type (WT) and AMPK double-knockout (DKO) MEF cells were treated with 1,1-DEE for 30 minutes. Similar to the results in AC16 cells, WT MEF cells showed increased AMPK and ACC phosphorylation upon 1,1-DEE treatment, while AMPK DKO MEF cells did not show this increase (Figure 3C). Furthermore, pretreatment with the AMPK inhibitor compound C reduced phosphorylation at the Ser483 residue of PFKFB2, confirming that PFKFB2 activation is dependent on 1,1-DEE-induced AMPK activation (Figure 3D). 【0179】 4. Confirm whether 1,1-DEE-induced AMPK activation is mediated by ROS. AMPK activation is primarily promoted by changes in ADP / ATP and AMP / ATP ratios. However, various studies have reported that AMPK can be activated by ROS, particularly H2O2. Therefore, we conducted experiments to confirm whether AMPK is activated by ROS production. 【0180】 After treatment with 1,1-DEE, ROS levels were measured using DCFH-DA and analyzed by fluorescent staining of live cells. The results showed that intracellular ROS levels increased after 10 minutes of treatment with 1,1-DEE compared to the control group (Figure 4A). Furthermore, pretreatment with the ROS scavenger NAC (N-acetylcysteine) was shown to reduce ROS production induced by 1,1-DEE (Figure 4A). 【0181】 Next, after pretreatment with NAC and ebselen, AMPK phosphorylation levels were analyzed via Western blotting after exposure to 1,1-DEE for 30 minutes. The results showed that AMPK phosphorylation decreased when ROS scavengers were used, indicating that ROS scavengers inhibit AMPK activation (Figure 4B). 【0182】 5. Confirm whether long-term treatment with 5.1,1-DEE increases PGC-1α expression through AMPK activation. In this study, we evaluated the level of AMPK activation during long-term exposure to 1,1-DEE. When AC16 cells were treated with 15 mM 1,1-DEE for 8 hours, AMPK phosphorylation increased at 4 and 8 hours, confirming AMPK activation (Figure 5A). 【0183】 Among AMPK targets, PGC-1α is a crucial factor that regulates most genes involved in mitochondrial metabolism and is considered a core regulator of mitochondrial biosynthesis. When AC16 cells were treated with 1,1-DEE for 8 hours, mRNA expression of the gene encoding PGC-1α, PPARG1Ca, increased (Figure 5B), and Western blot analysis confirmed that 1,1-DEE-induced AMPK activation increased PGC-1α expression (Figure 5C). 【0184】 To determine whether increased PGC-1α expression is regulated by AMPK activation, wild-type (WT) and AMPK double-deficient (DKO) MEF cells were treated with 15 mM 1,1-DEE for up to 12 hours. The results showed that 1,1-DEE-induced AMPK phosphorylation in WT MEF cells was associated with increased PGC-1α expression starting at 2 hours, but no difference in PGC-1α expression was observed in AMPK DKO MEF cells (Figure 5D). 【0185】 6. Elucidation of the mechanism of mitochondrial biosynthesis regulation by AMPK-induced PGC-1α PGC1-α is a key transcription factor that regulates mitochondrial biosynthesis and increases the amount of mitochondria through transcriptional machinery. PGC-1α binds to Nrf1 and Nrf2, increasing the transcription levels of mitochondrial genes associated with the electron transport chain (ETC) complex, while simultaneously promoting the expression of Tfam, which is responsible for mitochondrial transcription and gene replication. This enables the formation of new mitochondria. 【0186】 AC16 cells were treated with 15 mM 1,1-DEE for up to 8 hours to evaluate whether PGC-1α induces mitochondrial biosynthesis via the Nrf1 / Nrf2-Tfam axis. Semi-quantitative PCR and qRT-PCR results showed that mRNA expression of Nrf1 and Nrf2 increased after 8 hours of treatment, while Tfam expression significantly increased from 4 hours (Figure 6A). Western blot analysis also showed a significant increase in protein expression of Nrf2 and Tfam, but not of Nrf1 (Figure 6B). 【0187】 To confirm whether AMPK modulates increased expression of the Nrf1 / Nrf2-Tfam axis, wild-type (WT) and AMPK double-knockout (DKO) MEF cells were treated with 15 mM 1,1-DEE for up to 8 hours. As a result, Nrf1 and Nrf2 protein expression increased in WT MEF cells, but no difference was observed in AMPK DKO cells (Figure 6C). 【0188】 When AC16 cells were pretreated with the AMPK inhibitor compound C, Tfam protein expression was suppressed during 1,1-DEE exposure, confirming that mitochondrial biosynthesis via the Nrf1 / Nrf2 / Tfam axis is dependent on 1,1-DEE-induced AMPK activation (Figure 6D). 【0189】 Flow cytometry using MitoTracker Red showed that exposure of AC16 cells to 1,1-DEE increased the fluorescence signal and indicated an increase in mitochondria, while the signal decreased compared to compound C pretreatment (Figure 6F). Confocal microscopy revealed fragmented mitochondria (green arrows) observed during 1,1-DEE treatment, and this fragmentation decreased during compound C pretreatment. No such changes were observed with 1,2-DEE treatment (Figure 6E). 【0190】 II. Insulin Resistance <Materials and Methods> 1.Material The four ethanol batches used in this study are shown in Table 1 below. 1,1-DEE (A902), N-ethylmaleimide (NEM, E3876), N-acetyl-L-cysteine ​​(NAC, A9165), 2',7'-dichlorofluorescein diacetate (DCFH-DA; 35845), and H2O2 solution (88579) were purchased from Sigma-Aldrich (St. Louis, MO, USA). 1,2-DEE (D0456) was purchased from Tokyo Chemical Industry (Tokyo, Japan). 【0191】 [Table 2] 【0192】 2. Cell culture, 1,1-DEE treatment, and transient transfection with HA-tagged pCGN vector. C2C12, MEF, and Ea.hy926 cells were cultured in DMEM (Dulbecco-Modified Eagle's Medium, LM001-05) and supplemented with 10% (v / v) fetal bovine serum (FBS, S001-01) and 1% (v / v) penicillin / streptomycin (P / S, LS202-02) purchased from Welgene (Gyeongsan, Republic of Korea). AC16 cells were cultured in DMEM / Nutrient Mixture F-12 (DMEM / F12, LM002-05) and supplemented with 12.5% ​​(v / v) FBS and 1% (v / v) P / S purchased from Welgene. Once the cells reached a density of 70%, they were inoculated into 6-well plates and allowed to adhere overnight. 1,1-DEE was diluted to the specified concentration with serum-free DMEM before cell treatment. 【0193】 For transient transfection, cells were seeded into 6-well plates and left to adhere overnight. Cells were then transfected with HA-tagged pCGN PTEN vectors containing WT, C71S, C124S, or C71S / C124S using Lipofectamine 2000 (#11608-027, Invitrogen, Waltham, MA, USA) according to the manufacturer's protocol. In summary, DNA and Lipofectamine 2000 were separately mixed with Opti-MEM (reference: 31985-070, Gibco Life Technologies, Grand Island, NY, USA) and cultured at room temperature (RT) for 5 minutes. After combining the mixtures, they were cultured further at room temperature for 20 minutes. Cells were then treated with the mixture and cultured at 37°C under 5% CO2 conditions for 6 hours. The medium was then replaced with serum-containing DMEM, and the cells were cultured further. One day after transfection, the cells were treated with 1,1-DEE at a predetermined concentration and used for various analyses. 【0194】 3. Gas chromatography-mass spectrometry (GC-MS) Gas sampling The researchers used a continuous irrigation system for transurethral resection of the prostate (TURP) and vaporization. Gas generated during the cutting and cauterization processes collected in the upper part of the bladder. The mixture of solution and gas used for irrigation was drawn into a large container connected to a vacuum pump via a tube. A portion of the gas collected above the fluid in the container was guided from the exhaust gas outlet into a tube connected to a Tenax adsorption tube (Tenax GR; Japan Analytical Industry, Tokyo, Japan). The gas flow rate into the Tenax adsorption tube was maintained at 0.05 L / min using a gas flow pump (MP-S30; SIBATA, Tokyo, Japan). Measurements using a Tedlar Bag (Sigma-Aldrich) indicated that approximately 45 L of gas-room air mixture was produced per hour. For quantification, 1 L of surgical gas was injected into the Tenax adsorption tube at a flow rate of 0.05 L / min. 【0195】 Gas analysis Gas samples were purged and trapped using an Automated Purge & Trap Sampler JTD-505III (Japan Analytical Industry). Quantitative and qualitative analysis was performed using GC / MS QP 2010 Plus (Shimadzu, Kyoto, Japan). 【0196】 Purge and trap conditions The purging and trapping conditions are as follows: 【0197】 Desorption temperature: 280°C, Desorption time: 30 minutes, Desorption gas flow rate: 50 mL / min, Cold trap temperature: -40°C, Pyrolysis temperature: 280°C, Transfer line temperature: 280°C, Needle heater temperature: 280°C, Cold trap heater temperature: 200°C, Head press: 86 MPa, Column flow rate: 1.0 mL / min, and Splitting ratio: 1 / 100. 【0198】 GC / MS conditions The analysis conditions are as follows: 【0199】 Column: DB-624 column (30m x 0.251mm x 1.40μm; Agilent Technologies, Wilmington, DE, USA), Scan range: 30-600 mass, Oven temperature program: 40°C (held for 3 minutes), increase at 10°C / min to 260°C, then held for 5 minutes, Ion source temperature: 200°C, Transmission line temperature: 250°C, Electron energy (EM voltage): 70eV. 【0200】 4.Lyophilization Ethanol samples were stored in 15 mL Falcon tubes and then frozen at -80°C for 5 hours. Afterward, small holes were punctured in the caps of all Falcon tubes. The frozen samples were freeze-dried overnight to completely remove volatile and water-containing components. The following day, the contents of each Falcon tube were reconstituted with serum-free DMEM before cell processing. 【0201】 5. DCFH-DA staining for ROS detection Total intracellular reactive oxygen species (ROS) levels were assessed according to a previous study [Kim, H. and X. Xue, Detection of Total Reactive Oxygen Species in Adherent Cells by 2',7'-Dichlorodihydrofluorescein Diacetate Staining. J Vis Exp, 2020(160)]. Briefly, cells were dispensed into 6-well plates and cultured overnight at 5% CO2 37°C. After treatment, cells were washed once with serum-free DMEM and then cultured at 37°C in 10 μM DCFH-DA for 30 minutes. Subsequently, cells were washed once with serum-free DMEM and then twice with PBS. Finally, cells were rapidly imaged using a fluorescence microscope. 【0202】 6. Flow cytometry Intracellular reactive oxygen species (ROS) and mitochondrial peroxide levels were determined using flow cytometry (FACS CANTO II, BD Biosciences, NJ, USA). After 1,1-DEE treatment, cells were cultured with a predetermined concentration of DCFH-DA at 37°C for 30 minutes. Subsequently, cells were collected with Trypsin-EDTA (#25300-062, Gibco) and washed with cold PBS. Intracellular ROS levels were excited at 485 nm and released at 530 nm for immediate quantification, while mitochondrial peroxide levels were excited at 510 nm and released at 580 nm for quantification. 【0203】 7. Western blot analysis and antibodies The redox state of PTEN was analyzed according to the method described above. In summary, cells were dissolved in a lysis buffer containing 20 mM Tris-HCl (pH 7.5), 150 mM NaCl, 5% glycerol, 0.1% NP-40, a phosphate hydrolase inhibitor, a protease inhibitor, and 10 mM NEM. After sonication of the cell lysates, they were centrifuged at 13,000 rpm for 10 minutes. The supernatant was then collected and the protein concentration was measured using the Pierce® BCA Protein Quantification Kit (Thermo Fisher Scientific, Waltham, MA, USA). The lysates were mixed with a reducing sample buffer containing 60 mM Tris (pH 6.8), 25% glycerol, 2% SDS, 5% 2-mercaptoethanol, and 0.5% bromophenol, or a non-reducing sample buffer without 2-mercaptoethanol. Subsequently, the samples were subjected to SDS-PAGE and immunoblotting using PTEN-specific antibodies. 【0204】 To investigate the expression of other proteins, cell lysates were mixed with the described reducing sample buffer, followed by SDS-PAGE and immunoblotting with various specific antibodies. The antibodies used in this study were as follows: Akt (#9272S, 1:1000), phospho-Akt473 (#9271S, 1:1000), phospho-Akt308 (#9275S, 1:1000), phospho-PFKFB2 (Ser483) (#13064, 1:1000), PFKFB2 (#13029, 1:1000), and β-Actin (#4970, 1:1000). These antibodies were purchased from Cell Signaling Technology (Danvers, MA, USA). The GAPDH antibody (LF-PA0212, 1:1000) and the anti-rabbit IgG horseradish peroxidase-conjugated antibody (LF-SA8002, 1:5000) were purchased from Ab Frontier (Daejeon, Republic of Korea). 【0205】 8.Statistical analysis Western blot protein bands were quantified by densitometry using ImageJ 1.50i (National Institutes of Health, Bethesda, MD, USA). All values ​​were expressed as the mean ± standard error of the mean (SEM) of three independent experiments. Statistical significance was analyzed by 2-factor ANOVA for multigroup comparisons using GraphPad Prism, version 6 (GraphPad, San Diego, CA, USA). A p-value <0.05 was considered statistically significant. 【0206】 <Result> 1. Evaluation of the effect of ethanol batches of 1,1-DEE on PTEN oxidation. This study evaluated the effects of various ethanol batches from commercial sources on the redox state of PTEN. HepG2 cells were used in the experiments, and the effects of ethanol batches of different concentrations on the PTEN oxidation rate were investigated. The results showed significant differences in the PTEN oxidation rate depending on the ethanol batch, even at the same concentration. In particular, batch E1 induced PTEN oxidation more strongly than batches E2 and E3. Furthermore, when E1 was mixed with E2 or E3, the PTEN oxidation level tended to decrease compared to the PTEN oxidation effect of E1 alone (Figure 7A). 【0207】 Furthermore, it was confirmed that the odor characteristics of batch E1 were distinctly different from those of the other ethanol batches. Batch E1 exhibited strong alcoholic and fruity aromas, while these aromas were relatively less pronounced in batches E2 and E3. This suggests that certain compounds in batch E1 may affect the redox state of PTEN. 【0208】 To elucidate the compound characteristics of batches E1, E2, and E4, volatile compounds in each batch were analyzed. Batch E4 exhibited similar odor characteristics to E1 (Figure 7B). To confirm this, 100 mM ethanol was freeze-dried to evaporate the volatile compounds, and the dried samples were reconstituted in PBS or 100 mM E2. Subsequently, HepG2 cells were treated with the ethanol from each batch (100 mM, E1, E2, E4) or the corresponding dried sample for 10 minutes. The experimental results showed that batches E1 and E4 induced PTEN oxidation more strongly than E2 and the control group. However, the dried samples of E1, E2, and E4 did not show similar effects regardless of the reconstitution conditions (PBS or E2) (Figure 7C). This indicates that the volatile compounds evaporated during the freeze-drying process. 【0209】 Subsequently, GC-MS analysis identified additional compounds in batches E1, E2, E3, and E4. The analysis revealed that the aromatic compound 1,1-DEE (1,1-diethoxyethane) was expressed at high concentrations in E1 and E4, but not detected in E2 and E3. The results of GC-MS-based fragmentation analysis and the identified chemical structures of 1,1-DEE in batches E1 and E4 are shown in Figure 7D. Therefore, it was demonstrated that 1,1-DEE may play a novel role in the cellular function of mediating the redox regulation of PTEN. 【0210】 2.1,1-DEE evaluates whether it induces PTEN oxidation in a concentration-dependent manner. To determine if 1,1-DEE can exhibit novel molecular functions through the regulation of the redox state of PTEN, cells were treated with various concentrations of 1,1-DEE and PTEN oxidation levels were evaluated. 1,1-DEE-mediated PTEN oxidation was observed 10 minutes after treatment in various cell lines, including C2C12, MEF, AC16, and Ea.hy926. In C2C12 and MEF cells, PTEN oxidation was induced after treatment with 1 mM 1,1-DEE, while AC16 and Ea.hy926 cells achieved similar levels of oxidation with 5 mM 1,1-DEE (Figure 8A). 1,1-DEE-mediated oxidation occurred in a concentration-dependent manner, with oxidation levels increasing with increasing concentration. In contrast, 1,2-DEE, an isomer of 1,1-DEE, did not induce PTEN oxidation in C2C12 cells at various concentrations. This suggests a specific morphologically dependent function of 1,1-DEE in the redox regulation of PTEN (Figure 8B). 【0211】 To investigate the underlying mechanism of 1,1-DEE-mediated PTEN oxidation, C2C12 cells were transfected with HA-tagged pCGN vectors containing broad-spectrum (WT) PTEN or PTEN mutations (C71S, PTEN C124S, or PTEN C71 / 124S) before treatment with 1,1-DEE. PTEN oxidation was detected in cells transfected with WT PTEN, but not in cells transfected with PTEN C71S, PTEN C124S, or PTEN C71 / 124S (Figure 8C). This suggests that 1,1-DEE induces disulfide bond formation between Cys124 and Cys71 residues, mediating oxidative inactivation of PTEN. 【0212】 3. Evaluate whether 1,1-DEE induces PTEN oxidation in a time-dependent manner. This study investigated the time-dependent regulatory pattern of 1,1-DEE on the redox state of PTEN. Various cell types, including C2C12, MEF, AC16, and Ea.hy926, were treated with 1,1-DEE for 120 minutes. Interestingly, PTEN oxidation levels began to increase 5 minutes after the start of 1,1-DEE treatment, peaking at 10 minutes, and then gradually returning to basal levels after 120 minutes (Figure 9A). However, 1,2-DEE did not induce PTEN oxidation in C2C12 cells even after 120 minutes of treatment (Figure 9B). Therefore, it was demonstrated that a specific form of 1,1-DEE can induce reversible oxidation of PTEN in a time-dependent manner. 【0213】 4.1 Evaluation of the modulation of PTEN oxidation and associated Akt activation by 1-DEE This study investigated Akt activation induced by 1,1-DEE-induced PTEN oxidation. C2C12 cells were treated with various concentrations of 1,1-DEE for 10 minutes each, or with 10 mM 1,1-DEE for varying durations, for a total of 120 minutes. Akt phosphorylation at Ser473 and Thr308 was shown to be enhanced after treatment with 1 mM 1,1-DEE for 10 minutes, suggesting increased Akt activity. Akt phosphorylation was increased in a concentration-dependent manner by 1,1-DEE, indicating negative regulation of PTEN in the Akt signaling pathway (Figure 10A). Furthermore, it was confirmed that Akt phosphorylation at Ser473 and Thr308 is reversible, as is the reversible oxidation of PTEN mediated by 1,1-DEE. The levels of phosphorylated Akt473 and Akt308 increased within 5 minutes after 1,1-DEE treatment, peaking at 10 minutes, and then gradually returning to baseline levels after 120 minutes (Figure 10B). This suggests that oxidative inhibition of PTEN induced by 1,1-DEE may lead to reversible activation of Akt. 【0214】 5.1. Evaluate whether PTEN oxidation induced by ROS production is mediated by ROS production. In this study, to investigate the underlying mechanism of 1,1-DEE-induced PTEN oxidation, we evaluated ROS production levels in cells treated with 1,1-DEE. DCFH-DA staining revealed an increase in cytoplasmic ROS levels 10 minutes after 1,1-DEE treatment compared to the control group (Figure 11A). Flow cytometry showed that ROS levels increased 5 minutes after treatment, peaked at 10 minutes, and returned to baseline levels after 30 minutes. This indicates that 1,1-DEE can reversibly increase ROS production (Figure 11B). 【0215】 Next, to analyze the relationship between ROS production and 1,1-DEE-induced PTEN oxidation, cells were pretreated with the ROS scavenging agent NAC for 120 minutes, followed by treatment with 1,1-DEE. NAC pretreatment was confirmed to reduce 1,1-DEE-induced PTEN oxidation. This suggests that ROS produced by 1,1-DEE mediates the oxidative inactivation of PTEN. NAC pretreatment also reduced Akt phosphorylation levels at Ser473 and Thr308 (Figure 11C). These results suggest a regulatory mechanism for 1,1-DEE-induced ROS production in the PTEN / Akt signaling pathway. 【0216】 6.1,1-DEE is evaluated to determine whether it promotes glycolysis via Akt activation. Akt activation is known to regulate the rate of glycolysis via phosphorylation of PFKFB2 (6-phosphofructo-2-kinase / fructose-2,6-biphosphatase 2) at the Ser483 residue. PFKFB2 is a dual-function enzyme involved in both the synthesis and degradation of Fru-2,6-P2 (fructose-2,6-biphosphate), which controls glycolysis in eukaryotes. Phosphorylation of PFKFB2 enhances its activation, produces Fru-2,6-P2, and further improves the control of glycolysis. Therefore, to investigate the effect of Akt activation on glycolysis, we evaluated PFKFB2 phosphorylation at Ser483 in AC16 cells. The results showed that 1,1-DEE treatment increased PTEN oxidation and Akt activation via phosphorylation at Ser473, and PFKFB2 phosphorylation occurred at the Ser483 residue after 5 minutes of exposure to 1,1-DEE (Figure 12A). 【0217】 To determine whether PFKFB2 Ser483 phosphorylation is regulated by Akt activation, AC16 cells were pretreated with the Akt inhibitor MK-2206 and then treated with 1,1-DEE. MK-2206 pretreatment reduced both Akt activation and PFKFB2 phosphorylation, indicating that glycolysis may be regulated by 1,1-DEE-induced Akt activation (Figure 12A). 【0218】 Next, to examine the relationship between 1,1-DEE-induced ROS production and glycolysis, cells were pretreated with Ebselen. Interestingly, Ebselen pretreatment reduced the increase in 1,1-DEE-induced PFKFB2 phosphorylation (Figure 12B). These results suggest that 1,1-DEE-induced ROS production may further increase glycolysis via PFKFB2 phosphorylation, mediated by oxidative inactivation of PTEN and Akt activation. 【0219】 7.1,1-DEE is evaluated to determine whether it improves insulin sensitivity and reduces palmitate-induced insulin resistance. This study investigated the effects of 1,1-DEE on insulin signaling and insulin sensitivity in C2C12 cells. Treatment with 1,1-DEE induced PTEN oxidation and Akt activation, which were evaluated by phosphorylated Akt473 and phosphorylated Akt308 levels. Co-treatment of cells with 1,1-DEE and insulin resulted in increased Akt phosphorylation at Ser473 and Thr308 compared to treatment with 1,1-DEE or insulin alone (Figure 13A). This suggests that 1,1-DEE may enhance insulin signaling and insulin sensitivity. 【0220】 To evaluate the effect of 1,1-DEE on insulin resistance regulation, an in vitro cell model of insulin resistance was established using palmitic acid. These cells were treated with either 1,1-DEE or insulin for 10 minutes. A significant decrease in Akt phosphorylation at Ser473 and Thr308 residues was observed in insulin-resistant cells compared to control cells (Figure 7B). This indicated that an insulin resistance model was successfully produced through palmitic acid treatment. Importantly, co-administration of 1,1-DEE and insulin resulted in upward regulation of Akt phosphorylation in insulin-resistant cells (Figure 13B). This suggests that 1,1-DEE can alleviate palmitic acid-induced insulin resistance by mediating Akt activation. 【0221】 III. Obesity <Materials and Methods> 1. Animal Model and Oral Administration of 1,1-DEE Eight-week-old male C57BL-6J mice were purchased from Damool Science (Daejeon, Korea). The mice were divided into four groups (n = 5) and provided with various diets including a normal diet (ND) group, an ND group with 1,1-DEE administration, a high-fat diet (HFD) group, and an HFD group with 1,1-DEE administration (Figure 1). ND contained 10 kcal% fat, 70 kcal% carbohydrates, and 20 kcal% protein, while HFD contained 60 kcal% fat, 20 kcal% carbohydrates, and 20 kcal% protein. The mice were orally administered 100 mg / kg of 1,1-DEE once every two days, and the control group ingested the same amount of water. After 8 weeks of treatment, the mice were used for glucose tolerance and insulin tolerance tests. After 10 weeks of treatment, the mice were sacrificed to collect blood samples, which were stored at room temperature (RT) for 30 minutes. Liver, WAT, large intestine, and heart tissues were collected and rapidly immersed in liquid nitrogen, and then stored at -80 °C for further investigation. 【0222】 2. Serum Chemical Analysis After blood coagulation at RT, the blood samples were centrifuged at 3,000 rpm at 4 °C for 20 minutes, and the serum samples were transferred to Eppendorf tubes. Serum chemical analysis was performed using an automated blood chemistry analyzer ((Duyeol Biotech Company, Seoul, Republic of Korea), which included markers for lactate dehydrogenase (LDH), total bilirubin (T-Bili), total cholesterol (T-chol), triglyceride (TG), albumin (Alb), LDL-cholesterol (LDL-C), and HDL-cholesterol (HDL-C). Plasma insulin values were measured using a mouse insulin ELISA kit (#292-89401, FUJIFILM Wako Pure Chemical Corporation, Japan). 【0223】 3. Intraperitoneal Glucose Tolerance (IGTT) and Insulin Tolerance Test (IITT) For the glucose tolerance test, mice were transferred to new cages without food overnight for 12 hours. Fasting blood glucose levels were measured using a glucose meter. Subsequently, mice were intraperitoneally injected with 2 g / kg of D-glucose. Blood glucose levels were measured at 15, 30, 60, 90, and 120 minutes after glucose injection. For the insulin tolerance test, mice were fasted for 4 hours. Mice were intraperitoneally injected with insulin (Humulin R) at a dose of 0.6 U / kg. Blood glucose levels were recorded at 15, 30, 60, 90, and 120 minutes after insulin injection using a glucose meter. 【0224】 4. Histological analysis Liver, fat, large intestine, and heart tissues of each mouse were collected and fixed in 4% paraformaldehyde. After cutting the tissues into 5-mm thickness, they were embedded in paraffin. Paraffin sections were stained with hematoxylin and eosin (H&E). 【0225】 6. Western blot analysis Tissues were lysed using NP-40 lysis buffer (RIPA, 1% NP-40, 10 mM NEM). Tissue extracts were stored on ice for 1 hour and then centrifuged at 13,000 rpm for 30 minutes. The supernatant was collected, and the protein concentration was measured using a BCA kit. Reducing and non-reducing sample buffers were added to prepare the corresponding protein samples. Western blot was performed to investigate the protein expression of phosphorylated AMPK, AMPK, phosphorylated ACC, ACC, and β-actin. 【0226】 7. Statistical analysis Statistical analysis was performed using GraphPad Prism. Data were represented as mean ± standard error of the mean (SEM). Statistical significance was analyzed using two-way analysis of variance, and a p-value ≤ 0.05 was considered statistically significant. 【0227】 <Results> 1. Evaluation of the weight gain inhibitory effect of 1,1-DEE (1) Evaluation of the weight gain inhibitory effect of 1,1-DEE in high-fat diet (HFD) mice This study investigated the effect of 1,1-DEE on weight gain in an obesity model induced by a high-fat diet (HFD) (Figure 14). For the experiment, 8-week-old mice were orally administered an HFD supplemented with 100 mg / kg of 1,1-DEE every other day for 8 weeks. Figure 15A shows representative mice from each group. As a result, the HFD group showed significantly greater weight gain compared to the normal diet (ND) group, but the group administered 1,1-DEE significantly suppressed HFD-induced weight gain (Figure 15B). On the other hand, there was no difference in weight change between the ND group and the ND group supplemented with 1,1-DEE (Figure 15B), and while 1,1-DEE increased food intake in the ND group, food intake in the HFD group and the HFD+1,1-DEE group was maintained at similar levels (Figure 15). These results are interpreted as 1,1-DEE inducing appetite in mice. Furthermore, post-sacrificial tissue analysis showed that 1,1-DEE had the effect of reducing eWAT and iWAT body weight induced by HFD (Figure 15D-E). No significant differences were observed in the weight and length of the heart, liver, or colon (Figure 15F-H). 【0228】 (2) Evaluation of weight control by comparison of 1,1-DEE and metformin In addition, this study conducted additional experiments comparing the anti-obesity effects of 1,1-DEE and metformin. First, in a high-fat diet (HFD) mouse model, 1,1-DEE rapidly suppressed weight gain from the initial stages of administration, and the weight loss effect was sustained for 4 weeks compared to the HFD group. On the other hand, the metformin-treated group showed a slight weight gain in the first week, but thereafter the rate of weight gain was gradually regulated. In normal diet (ND) mice, 1,1-DEE administration did not affect weight changes. In particular, mice treated with 1,1-DEE in the HFD+D100 group showed increased food intake compared to the HFD group, suggesting that 1,1-DEE may exert its effect on weight regulation through exercise mimetic action rather than appetite suppression. These results indicate that 1,1-DEE can suppress weight gain more rapidly than metformin (Figure 16). Therefore, we confirmed that 1,1-DEE can be utilized as a useful candidate substance for the prevention and treatment of obesity and diabetes-related metabolic diseases. 【0229】 2.1,1-DEE Evaluation of its effect on blood glucose control and insulin resistance improvement To evaluate the effects of 1,1-DEE on glucose and insulin metabolism, random blood glucose levels were measured every two weeks. The results showed that blood glucose levels were significantly lower in the 1,1-DEE-treated group compared to the HFD group (Figure 17A). After 8 weeks of treatment, fasting blood glucose levels measured after 12 hours of fasting were higher in the HFD group than in the ND group, indicating a decrease in fasting blood glucose with 1,1-DEE administration (Figure 17B). Furthermore, the HFD group supplemented with 1,1-DEE showed lower GTT(AUC) values ​​compared to the HFD group, confirming improved glucose tolerance (Figure 17C). This suggests that 1,1-DEE has a positive effect on glucose metabolism. After 8 weeks, serum insulin levels were higher in the HFD group compared to the ND group, indicating improved insulin levels in the 1,1-DEE-treated group (Figure 17D). In an insulin resistance test (ITT) to evaluate insulin resistance, the 1,1-DEE-treated group showed a lower AUC value and improved insulin sensitivity (p=0.2427, Figure 17E). Therefore, it was confirmed that 1,1-DEE can improve glucose metabolism and insulin sensitivity in hyperglycemic and insulin-resistant states. 【0230】 3.1,1-DEE Evaluation of its effects on improving liver damage and fat production To evaluate whether 1,1-DEE improves liver damage and fat production in HFD mice, serum biomarkers were analyzed. Liver damage-related biomarkers such as ALT, AST, and LHD were relatively increased in the HFD group, but decreased in the 1,1-DEE-treated group (Figures 18A-C). No significant differences were observed in serum ALP, T-Bil, and Alb levels (Figures 18D-F). Furthermore, when serum biomarkers such as TG, T-chol, HDL-C, and LDL-C were investigated, 1,1-DEE showed an effect of reducing TG levels in the HFD group (Figure 18G), and HFD-induced HDL-C and LDL-C levels decreased after 1,1-DEE treatment (Figures 18H-K). In particular, 1,1-DEE demonstrated that it can improve HFD-induced LDL-C levels and reduce the risk of arteriosclerosis (Figure 18K). These results suggest that 1,1-DEE can improve liver damage and fat production in obese mice induced by HFD. 【0231】 Issue-specific number: 2018R1D1A1B06051438 Ministry / Agency: Ministry of Science and ICT Research Management Specialist Agency: Korea Research Foundation Research project title: Regulation of the cancer-suppressing protein PTEN by alcohol Supervising institution: Chonnam National University Participating company: LUX ANIMA CO.,LTD. Research period: March 1, 2023 - February 29, 2024 Issue-specific number: 2022M3A9E4017151 Ministry / Agency: Ministry of Science and ICT Research Management Specialist Agency: Korea Research Foundation Research topic: Development of MyHeart Platform-based heart failure control and treatment technologies Supervising institution: Chonnam National University Participating company: LUX ANIMA CO.,LTD. Research period: January 2024 - December 2024 Ministry / Agency Name: Jeonnam Technopark Foundation Research Project Name: Support Project for Strengthening Knowledge Asset Capacity in the Huashun Vaccine Industry Special Zone Research subject name: IP-R&D Organizing body: LUX ANIMA CO.,LTD. Although specific parts of the present invention have been described in detail above, it will be clear to those with ordinary skill in the art that such specific technologies are merely preferred examples and do not limit the scope of the present invention. Therefore, the substantial scope of the present invention is defined by the appended claims and their equivalents.

Claims

[Claim 1] An AMPK (AMP-activated protein kinase) activator containing 1,1-diethoxyethane (1,1-DEE) as the active ingredient. [Claim 2] The 1,1-diethoxyethane is characterized by inducing phosphorylation of the Ser172 residue of AMPK, thereby promoting fatty acid oxidation or suppressing fatty acid production, and promoting glucose breakdown or suppressing glucose neogenesis through glycolysis regulation, as described in claim 1. [Claim 3] The 1,1-diethoxyethane is characterized by temporarily suppressing oxidative phosphorylation (OXPHOS) and activating AMPK through the production of ROS (reactive oxygen species), as described in claim 1. [Claim 4] The AMPK activator according to claim 1, characterized in that the 1,1-diethoxyethane promotes bioenergy ATP biosynthesis. [Claim 5] The AMPK activator according to claim 1, characterized in that the 1,1-diethoxyethane increases PGC-1α (peroxisome proliferator-activated receptor gamma coactivator-1 alpha) expression and promotes mitochondrial biosynthesis. [Claim 6] A pharmaceutical composition for the prevention or treatment of diseases requiring AMPK (AMP-activated protein kinase) activation, comprising 1,1-diethoxyethane (1,1-DEE) as an active ingredient, A pharmaceutical composition characterized in that the disease requiring AMPK activation includes one or more selected from nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), liver fibrosis, dyslipidemia, arteriosclerosis, hypertension, ischemic heart disease, inflammatory bowel disease, and rheumatoid arthritis. [Claim 7] An anti-aging cosmetic composition containing 1,1-diethoxyethane (1,1-DEE) as an active ingredient. [Claim 8] A food composition containing 1,1-diethoxyethane (1,1-DEE) as an active ingredient for the prevention or improvement of diseases requiring AMPK (AMP-activated protein kinase) activation, anti-aging, life extension, or enhancement of physical vitality. [Claim 9] A feed composition containing 1,1-diethoxyethane (1,1-DEE) as an active ingredient for the prevention or improvement of diseases requiring AMPK (AMP-activated protein kinase) activation, as well as for anti-aging, life extension, or enhancement of physical vitality. [Claim 10] A composition for increasing insulin sensitivity or improving insulin resistance, comprising 1,1-diethoxyethane (1,1-DEE) as an active ingredient. [Claim 11] The composition for increasing insulin sensitivity or improving insulin resistance according to claim 10, characterized in that the 1,1-diethoxyethane induces oxidative inactivation of PTEN through the formation of a disulfide bond between Cys124 and Cys71 residues of PTEN. [Claim 12] The 1,1-diethoxyethane is characterized by increasing phosphorylation at Ser473 and Thr308 of Akt, thereby activating Akt, as described in claim 10, for increasing insulin sensitivity or improving insulin resistance. [Claim 13] The 1,1-diethoxyethane is characterized in that it increases phosphorylation at the Ser483 residue of PFKFB2 (6-phosphofructo-2-kinase / fructose-2,6-biphosphophosphate 2) and promotes glycolysis, as described in claim 10, for increasing insulin sensitivity or improving insulin resistance. [Claim 14] A pharmaceutical composition for the prevention or treatment of insulin resistance-related diseases, comprising 1,1-diethoxyethane (1,1-DEE) as an active ingredient, Diseases related to insulin resistance include: Type 1 diabetes, Type 2 diabetes, Impaired Glucos Tolerance (IGT), Impaired Fasting Glucosity (IFG), Hyperglycemia, Postprandial Hyperglycemia, Polycystic Ovary Syndrome (PCOS), Hyperlipidemia, and Fasting Plasma. Blood glucose dysregulation, including decreased postprandial plasma glucose (PPG), and / or glycated hemoglobin (HbA1c) and improved blood glucose regulation; diabetes progression-related disorders, including prevention, slowing, delaying, or reversal of progression from impaired glucose tolerance (IGT), impaired fasting glucose (IFG), insulin resistance, or metabolic syndrome to type 2 diabetes; cataracts, microvascular and macrovascular diseases. Diabetic complications including diseases, nephropathy, retinopathy, neuropathy, tissue ischemia, diabetic foot disease, acute coronary syndrome, peripheral artery occlusive disease, cardiomyopathy, and vascular restenosis; weight loss, prevention of weight gain, or promotion of weight loss Weight management disorders, including weight loss;A pharmaceutical composition characterized by comprising one or more selected from the following: pancreatic beta-cell related disorders, including prevention, slowing, delaying, or treating pancreatic beta-cell degeneration and / or pancreatic beta-cell dysfunction; improvement and / or restoration of pancreatic beta-cell function; and / or restoration of pancreatic insulin secretory function; and insulin-related disorders, including maintenance and / or improvement of insulin sensitivity; and prevention or treatment of hyperinsulinemia and / or insulin resistance. [Claim 15] A cosmetic composition for the prevention or improvement of diseases related to insulin resistance, comprising 1,1-diethoxyethane (1,1-DEE) as an active ingredient. [Claim 16] A food composition for the prevention or improvement of diseases related to insulin resistance, comprising 1,1-diethoxyethane (1,1-DEE) as an active ingredient. [Claim 17] A feed composition for the prevention or improvement of diseases related to insulin resistance, comprising 1,1-diethoxyethane (1,1-DEE) as an active ingredient. [Claim 18] A pharmaceutical composition for the prevention or treatment of obesity or obesity-related diseases, comprising 1,1-diethoxyethane (1,1-DEE) as an active ingredient. [Claim 19] A cosmetic composition for the prevention or improvement of obesity or obesity-related diseases, comprising 1,1-diethoxyethane (1,1-diethoxyethane, 1,1-DEE) as an active ingredient. [Claim 20] A food composition for the prevention or improvement of obesity or obesity-related diseases, comprising 1,1-diethoxyethane (1,1-DEE) as an active ingredient. [Claim 21] A feed composition for the prevention or improvement of obesity or obesity-related diseases, comprising 1,1-diethoxyethane (1,1-DEE) as an active ingredient.

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