Medicine for preventing and treating obesity and application thereof

Abstract

The invention discloses a medicine for preventing and treating obesity and application of the medicine. Akebia saponin D is used for preventing and treating obesity by promoting beige of white fat and activation of brown fat and activating fat to generate heat. The medicine for preventing and treating obesity is composed of akebiaquinata saponin D and pharmaceutic adjuvants, the mass percentage of the akebiaquinata saponin D is 0.54%-2.83%, and the purity of the akebiaquinata saponin D is larger than or equal to 98%.

Description

Technical Field

[0001] The present invention relates to the technical field of medicine, and in particular to a medicine for preventing and treating obesity, and the specific use of the medicine. Background Art

[0002] In recent years, with the change of living habits, the high-sugar and high-fat diet has led to an increasing prevalence of obesity in the population. As early as 1948, obesity was defined as a disease. Currently, there are more than 700 million obese people in the world, and many overweight people are potential obese patients. Obesity is defined as the body's intake of more calories than consumption, resulting in excessive accumulation of body fat (mainly triglycerides), an increase in the number or size of fat cells, and the body mass index (BMI) is usually used to evaluate overweight or obesity. The World Health Organization defines BMI ≥ 25 as overweight and BMI ≥ 30 as obesity. Obesity is related to lipid accumulation and lipid metabolism dysfunction, develops slowly and is complicated by a variety of chronic diseases. Obesity is closely related to a variety of metabolic diseases and cardiovascular diseases, including non-alcoholic fatty liver, diabetes, and metabolic syndrome.

[0003] Fatty liver is a clinical syndrome characterized by diffuse fatty changes in liver cells caused by various inducing factors such as long-term drinking, drug-induced liver damage and long-term malnutrition. Metabolic syndrome refers to a pathological state in which the body's proteins, fats, carbohydrates and other substances undergo metabolic disorders, manifested as abdominal obesity or overweight, hyperglycemia, hyperlipidemia and hypertension accompanied by other metabolic comorbidities such as non-alcoholic fatty liver and diabetes. Obesity, fatty liver and metabolic syndrome have some common features, but there are also great differences. For example, metabolic syndrome is mainly abdominal obesity accompanied by other metabolic comorbidities, while obesity may be systemic obesity. The occurrence sites and mechanisms of the three diseases are different, so the drugs used for treatment are very different. Drugs that treat one of the diseases cannot treat another. For example, orlistat, a drug for the treatment of obesity, cannot play a role in lowering blood sugar and blood lipids, and cannot be used to treat metabolic syndrome. Silymarin, a drug for the treatment of non-alcoholic fatty liver, cannot reduce weight or prevent obesity.

[0004] Drug treatment for obesity has a tortuous history. To date, the FDA has approved more than a dozen weight-loss drugs, but many of them have been withdrawn from the market due to serious side effects. Among the currently marketed weight-loss drugs, phentermine / topiramate and naltrexone / bupropion all act on the central nervous system to achieve the purpose of weight loss by suppressing appetite and producing a sense of fullness. Long-term use can cause side effects such as anxiety, depression, and cognitive impairment. The GLP-1 receptor agonists liraglutide and semaglutide increase satiety, reduce appetite, and slow gastric emptying by inhibiting glucagon secretion. However, the inconvenience of subcutaneous injection limits the widespread use of the drug. At present, only orlistat is approved for the treatment of obesity in China. However, orlistat can cause liver damage and gastrointestinal adverse reactions (such as oily stools and a sense of urgency during bowel movements). In addition, the long-term cardiovascular risks of orlistat are still unclear. Based on the above safety considerations and effectiveness analysis, finding anti-obesity drugs from other mechanisms is a key issue that needs to be solved urgently.

[0005] Studies have shown that the browning of white fat and the activation of brown fat can promote the body's energy consumption and improve the body's metabolic disorders, and are new ways to treat obesity. White fat is divided into subcutaneous fat and visceral fat. In addition to storing lipid substances, subcutaneous white fat also has the ability to convert into beige fat to promote heat production. Beige fat and brown fat have similar morphology and function, and will activate heat production under certain conditions; while visceral fat beige heat production capacity is poor, and its main function is to store fat in the form of lipid droplets. In a cold environment or when the body is in motion, the sympathetic nerves secrete more norepinephrine (NE). After the β3 receptors on the surface of adipocytes receive NE signals, the nuclear transcription levels of HSL and UCP1 mRNA increase, and the translation and synthesis of HSL and UCP1 increase. HSL catalyzes the decomposition of triglycerides to produce free fatty acids as substrates for heat production. At the same time, UCP1 enters the mitochondria, decoupling protons from the mitochondrial respiratory transport chain, and some protons involved in ATP generation undergo ineffective circulation to generate heat. In addition, NE can also promote the beigeization of subcutaneous white fat. In the whole body adipose tissue of mice, activating thermogenesis in interscapular brown fat (BAT) and promoting beigeization of white fat in inguinal subcutaneous fat (iWAT) can both play a similar thermogenic function. Therefore, it is of great significance to explore the mechanism of beigeization of white fat and activation of brown fat, discover potential drug targets for the prevention and treatment of obesity, and find new drugs for the treatment of obesity.

[0006] Natural products have the characteristics of structural diversity, good activity and less toxic side effects. In addition, my country has a vast territory and abundant natural resources of Chinese medicinal materials, so it is very suitable as a source for the discovery of anti-obesity drugs.

[0007] Akebia saponin D, also known as Dipsaconin VI, is a triterpenoid saponin compound derived from the dried rhizome of Dipsacus asper. Dipsacus asper has the effects of nourishing the liver and kidneys, strengthening tendons and bones, healing fractures, and stopping metrorrhagia. Akebia saponin D is the main active ingredient of Dipsacus asper. Summary of the invention

[0008] In order to overcome the defects of the prior art, the technical problem to be solved by the present invention is to provide a drug for preventing and treating obesity. Akebia saponin D prevents and treats obesity by promoting beigeization of white fat and activating fat thermogenesis.

[0009] The technical scheme of the present invention is: the medicine used for preventing and treating obesity is composed of akebia saponin D and pharmaceutical excipients, the mass percentage of akebia saponin D is 0.54% to 2.83%, and the purity of akebia saponin D is ≥98%.

[0010] Preferably, the dosage of the akebia saponin D is 37.5-150 mg / kg / d.

[0011] Preferably, the preparation used is an oral liquid, powder, granule, or syrup.

[0012] Preferably, the pharmaceutical excipient is selected from any one of the following: lyophilized powder excipient, oral preparation excipient.

[0013] Also provided is the drug for use in high-fat diet obesity.

[0014] Also provided is the medicament for reducing the size, volume, and weight of white fat cells.

[0015] The invention also provides the drug for improving the insulin resistance state induced by a high-fat diet.

[0016] Also provided is the drug for changing the expression level of UCP1 mRNA of the white fat beige gene in fat cells and promoting the expression of UCP1 in brown fat tissue.

[0017] The drug is also provided for promoting beigeization of subcutaneous white fat and activation of brown fat, promoting the expression of heat-related genes, increasing the heat-generating capacity of fat cells, alleviating insulin resistance and increasing the utilization of blood sugar and blood lipids, and reducing lipid accumulation in adipose tissue. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1 This is the diagram showing the changes in the size of brown fat and white fat in mice after drug intervention;

[0019] Figure 2 This is the body weight curve of mice after drug intervention;

[0020] Figure 3This is a bar graph of fat weight after drug intervention in mice;

[0021] Figure 4A HE staining of iWAT adipose tissue cells in mice in the control group;

[0022] Figure 4B HE staining of iWAT adipose tissue cells in mice in the model group;

[0023] Figure 4C HE staining of iWAT adipose tissue cells in mice after intervention with Akebia saponin D 37.5mg / kg / d;

[0024] Figure 4D HE staining of iWAT adipose tissue cells in mice after intervention with Akebia saponin D 75mg / kg / d;

[0025] Figure 4E HE staining of iWAT adipose tissue cells in mice after intervention with Akebia saponin D 150mg / kg / d;

[0026] Figure 4F HE staining of iWAT adipose tissue cells in mice after metformin intervention;

[0027] Figure 5 Mouse insulin tolerance curve;

[0028] Figure 6 Mouse glucose tolerance curve;

[0029] Figure 7 Histogram of thermogenic gene expression in adipocytes differentiated from C3H10T1 / 2 cells;

[0030] Figure 8 WB image of UCP1 protein expression in mouse brown adipose tissue;

[0031] Fig. 9 Infrared temperature imaging of mice;

[0032] Fig.10 Mouse body surface temperature curve;

[0033] Fig.11 Mouse core temperature curve;

[0034] Fig.12 24h oxygen consumption curve of mice;

[0035] Fig.13 Histogram of oxygen consumption of mice for 24 h;

[0036] Fig.14 24h exhaled carbon dioxide curve of mice;

[0037] Fig.15Histogram of mouse exhaled carbon dioxide for 24 hours;

[0038] Fig.16 24h energy expenditure curve of mice;

[0039] Fig.17 Bar graph of 24-hour energy expenditure in mice. DETAILED DESCRIPTION

[0040] The embodiments of the present invention are described in detail below.

[0041] Example 1 The effects of Akebia saponin D on body weight and fat weight in an animal model of obesity induced by a high-fat diet were studied.

[0042] Experimental animals: C57BL / 6J mice, male, weight (25±2) g.

[0043] Experimental method: The mice were divided into 7 groups according to their body weight, so that there was no significant difference in body weight among the groups. The specific groupings were as follows: the first group of 5 mice was given normal feed and physiological saline as a blank control group; the second group of 5 mice was given a high-fat diet (Research diet D12492) and physiological saline as a model group; the third group of 5 mice was given a high-fat diet and 37.5 mg / kg / d of Akebia saponin D; the fourth group of 5 mice was given a high-fat diet and 75 mg / kg / d of Akebia saponin D; the fifth group of 5 mice was given a high-fat diet and 150 mg / kg / d of Akebia saponin D; the sixth group of 5 mice was given a high-fat diet and 300 mg / kg / d of metformin. The mice were given physiological saline or Akebia saponin D or metformin at the same time as the high-fat diet, 0.2 ml per mouse, and the administration was all done by gavage. All mice were free to eat and drink water, and the light cycle was 12 hours and the dark cycle was 12 hours. The weight of mice was recorded once a week, and the drug was administered for 12 consecutive weeks. The mice were anesthetized, and the eyeballs were removed to collect blood. Then, the mice were killed by cervical dislocation, and the adipose tissue was removed, photographed and weighed, and the organ coefficient was calculated based on the weight.

[0044] Solvent: Akebia saponin D and metformin were prepared with normal saline.

[0045] Detection indicators: Detect and compare the changes in body weight and fat weight of each group of mice after drug intervention. The fat is divided into: interscapular brown fat (BAT), epididymal white adipose tissue (eWAT) and inguinal subcutaneous fat (iWAT).

[0046] Test results: Combined Figures 1 to 3 It can be seen that Akebia saponin D inhibited the weight gain and fat accumulation induced by a high-fat diet.

[0047] Example 2 The effect of Akebia saponin D on the size of adipose tissue cells in an animal model of obesity induced by a high-fat diet was studied.

[0048] Experimental animals: C57BL / 6J mice, male, weight (25±2) g.

[0049] Experimental method: The mice were divided into 7 groups according to their body weight, so that there was no significant difference in body weight among the groups. The specific groupings were as follows: the first group of 5 mice was given normal feed and physiological saline as a blank control group; the second group of 5 mice was given a high-fat diet (Research diet D12492) and physiological saline as a model group; the third group of 5 mice was given a high-fat diet and 37.5 mg / kg / d of Akebia saponin D; the fourth group of 5 mice was given a high-fat diet and 75 mg / kg / d of Akebia saponin D; the fifth group of 5 mice was given a high-fat diet and 150 mg / kg / d of Akebia saponin D; the sixth group of 5 mice was given a high-fat diet and 300 mg / kg / d of metformin. The mice were given physiological saline or Akebia saponin D or metformin at the same time as the high-fat diet, with each mouse receiving 0.2 ml, and the administration was all done by gavage. All mice were free to eat and drink water, and the light cycle was 12 hours and the dark cycle was 12 hours. The weight of mice was recorded once a week, and the drug was given for 12 consecutive weeks. The mice were anesthetized, and the eyeballs were removed for blood collection. Then the mice were killed by cervical dislocation, and the adipose tissue was removed for subsequent HE staining analysis. The adipose tissue was fixed with 4% paraformaldehyde. After trimming, dehydration, transparency, wax immersion, and embedding, paraffin tissue sections were made, and the thickness of the sections was 4 to 6 μm. When HE staining, the paraffin in the sections was first removed with xylene, and the rinsed sections were placed in a hematoxylin aqueous solution for staining for several minutes. After rinsing with distilled water, the sections were differentiated with 1% hydrochloric acid ethanol for several seconds, and 0.6% ammonia water was turned blue for 15 minutes and then rinsed with running water. Eosin staining solution was added for staining for 30 seconds. The stained sections were dehydrated, transparent, fixed and sealed, and observed with an optical microscope.

[0050] Solvent: Akebia saponin D and metformin were prepared with normal saline.

[0051] Detection indicators: Detect and compare the changes in adipose tissue size and adipocyte HE staining of each group of mice after drug intervention.

[0052] Test results: Combined Figures 4A to 4F It can be seen that akebiasaponin D reduced the size of white adipocytes.

[0053] Example 3 The effects of Akebia saponin D on GTT and ITT in an animal model of obesity induced by a high-fat diet were studied.

[0054] Experimental animals: C57BL / 6J mice, male, weight (25±2) g.

[0055] Experimental method: The mice were divided into 7 groups according to their body weight, so that there was no significant difference in body weight among the groups. The specific groupings were as follows: the first group of 5 mice was given normal feed and physiological saline as a blank control group; the second group of 5 mice was given a high-fat diet (Research diet D12492) and physiological saline as a model group; the third group of 5 mice was given a high-fat diet and 37.5 mg / kg / d of Akebia saponin D; the fourth group of 5 mice was given a high-fat diet and 75 mg / kg / d of Akebia saponin D; the fifth group of 5 mice was given a high-fat diet and 150 mg / kg / d of Akebia saponin D; the sixth group of 5 mice was given a high-fat diet and 300 mg / kg / d of metformin. The mice were given physiological saline or Akebia saponin D or metformin at the same time as the high-fat diet, with each mouse receiving 0.2 ml, and the administration was all done by gavage. All mice were free to eat and drink water, and the light cycle was 12 hours and the dark cycle was 12 hours.

[0056] Glucose tolerance test: The glucose tolerance test was conducted on mice at 11 weeks. After the mice were fasted for 12 hours but not water, each mouse was intraperitoneally injected with a glucose solution at a dose of 1g / Kg. Each mouse was weighed, and the injection dose for a mouse weighing 10g was 0.1mL. Blood was collected from the tail vein at 0min, 15min, 30min, 60min, and 120min after the glucose injection to measure the blood glucose level of the mice.

[0057] Insulin tolerance test: Insulin tolerance test was conducted on mice at 11 weeks. After fasting for 4 hours, each mouse was intraperitoneally injected with 0.5U / Kg of glucose solution. Each mouse was weighed, and the injection dose for a mouse weighing 10g was 0.1mL. Blood was collected from the tail vein at 0min, 15min, 30min, 60min, and 90min after glucose injection to measure the blood glucose level of the mice.

[0058] Solvent: Akebia saponin D, metformin, glucose and insulin were all prepared with normal saline.

[0059] Detection indicators: Glucose tolerance test (GTT) and insulin tolerance test (ITT) were performed on mice, and the differences among the groups were compared.

[0060] Test results: Combined Figure 5 and Figure 6 As shown, it can be seen that Akebia saponin D improves the insulin resistance state induced by high-fat diet.

[0061] Example 4 The effects of Akebia saponin D on thermogenesis and beige marker genes of adipocytes differentiated from C3H10T1 / 2 cells were studied.

[0062] Experimental method: C3H10T1 / 2 cell culture and adipogenic differentiation induction. After the cell density reaches full, the cells are cultured for two days to allow the cells to exit the growth cycle. The differentiation medium (DMEM-HG + 10% FBS + 1% double antibody) is changed to culture for 2 days, recorded as day 0, and the differentiation medium is induced by adding inducers (3-isobutyl-1-methylxanthine 500μM, insulin 5μg / ml, indomethacin 50μM, dexamethasone 1μM). On the second day, the maintenance medium is changed to DMEM-HG + 10% FBS + 5μg / ml insulin and cultured for 2 days. Akebia saponin D is added to the differentiation medium to prepare 200μM, and the medium is changed every two days until the 8th day.

[0063] Drug preparation method: Weigh 185.82 mg of Akebia saponin D and dissolve it in 1 ml of DMSO to prepare 200 μM, then store it at -20°C after aliquoting.

[0064] Detection indicators: RNA was extracted from differentiated mature adipocytes placed on ice. RNA concentration was detected and quantified. RNA was converted into cDNA and fluorescent quantitative PCR was performed to detect the expression of target genes related to beigeization of white fat.

[0065] Test results: From Figure 7 It can be seen that Akebia saponin D changed the expression level of UCP1 mRNA, a beige gene in adipocytes, and the changes in many thermogenic genes.

[0066] Example 5: Detect the effect of akebia saponin D on the expression of UCP1 in brown adipose tissue.

[0067] Experimental animals: C57BL / 6J mice, male, weight (25±2) g.

[0068] Experimental method: The mice were divided into 7 groups according to their body weight, so that there was no significant difference in body weight among the groups. The specific groupings were as follows: the first group of 5 mice was given normal feed and physiological saline as a blank control group; the second group of 5 mice was given a high-fat diet (Research diet D12492) and physiological saline as a model group; the third group of 5 mice was given a high-fat diet and 37.5 mg / kg / d of Akebia saponin D; the fourth group of 5 mice was given a high-fat diet and 75 mg / kg / d of Akebia saponin D; the fifth group of 5 mice was given a high-fat diet and 150 mg / kg / d of Akebia saponin D; the sixth group of 5 mice was given a high-fat diet and 300 mg / kg / d of metformin. The mice were given physiological saline or Akebia saponin D or metformin at the same time as the high-fat diet, 0.2 ml per mouse, and the administration was all done by gavage. All mice were free to eat and drink water, and the light cycle was 12 hours and the dark cycle was 12 hours. The body weight of mice was recorded once a week, and the drug was administered for 12 consecutive weeks. The mice were anesthetized, and the eyeballs were removed to collect blood. Then, the mice were killed by cervical dislocation, and the adipose tissue was removed.

[0069] Solvent: Akebia saponin D and metformin were prepared with normal saline.

[0070] Detection indicators: separation of brown adipose tissue, BCA quantitative concentration, primary antibody at 4℃ overnight, secondary antibody incubation at 37℃ for 1h, Odyssey infrared laser imaging analysis system scanning results, gray value measurement. Tubulin (α-tubulin) as internal reference protein.

[0071] Test results: Combined Figure 8 It can be seen that Akebia saponin D can promote the expression of UCP1 in brown adipose tissue.

[0072] Example 6 Detect the effect of akebia saponin D on the body's adaptive heat production.

[0073] Experimental animals: C57BL / 6J mice, male, weight (25±2) g.

[0074] Experimental method: The mice were divided into 7 groups according to their body weight, so that there was no significant difference in body weight among the groups. The specific groupings were as follows: the first group of 5 mice was given normal feed and physiological saline as a blank control group; the second group of 5 mice was given a high-fat diet (Research diet D12492) and physiological saline as a model group; the third group of 5 mice was given a high-fat diet and 37.5 mg / kg / d of Akebia saponin D; the fourth group of 5 mice was given a high-fat diet and 75 mg / kg / d of Akebia saponin D; the fifth group of 5 mice was given a high-fat diet and 150 mg / kg / d of Akebia saponin D; the sixth group of 5 mice was given a high-fat diet and 300 mg / kg / d of metformin. The mice were given physiological saline or Akebia saponin D or metformin at the same time as the high-fat diet, with each mouse receiving 0.2 ml, and the administration was all done by gavage. All mice were free to eat and drink water, and the light cycle was 12 hours and the dark cycle was 12 hours.

[0075] Cold exposure experiment: After 12 weeks of administration, the mice were subjected to a cold exposure adaptive heat production experiment. The mice were continuously exposed to a 4°C environment. The body surface temperature was recorded using an infrared temperature imager and the rectal temperature was quickly measured using an electronic thermometer at 0h, 0.5h, 1h, 1.5h, 2.5h and 4h after the start of the cold stimulation.

[0076] Solvent: Akebia saponin D and metformin were prepared with normal saline.

[0077] Detection indicators: Measure the surface temperature and core temperature of mice.

[0078] Experimental results: From Fig. 9 , Fig.10 and Fig.11 It can be seen that the administration of Akebia saponin D promoted the ability of mice to adapt to cold environment.

[0079] Example 7 The effect of akebia saponin D on energy metabolism in an animal model of obesity induced by a high-fat diet was studied.

[0080] Experimental animals: C57BL / 6J mice, male, weight (25±2) g.

[0081] Experimental method: The mice were divided into 7 groups according to their body weight, so that there was no significant difference in body weight among the groups. The specific groupings were as follows: the first group of 5 mice was given normal feed and physiological saline as a blank control group; the second group of 5 mice was given a high-fat diet (Research diet D12492) and physiological saline as a model group; the third group of 5 mice was given a high-fat diet and 37.5 mg / kg / d of Akebia saponin D; the fourth group of 5 mice was given a high-fat diet and 75 mg / kg / d of Akebia saponin D; the fifth group of 5 mice was given a high-fat diet and 150 mg / kg / d of Akebia saponin D; the sixth group of 5 mice was given a high-fat diet and 300 mg / kg / d of metformin. The mice were given physiological saline or Akebia saponin D or metformin at the same time as the high-fat diet, 0.2 ml per mouse, and the administration was all done by gavage. All mice were free to eat and drink water, and the light cycle was 12 hours and the dark cycle was 12 hours.

[0082] Solvent: Akebia saponin D and metformin were prepared with normal saline.

[0083] Detection index: At 10-12 weeks, the mice in the blank control group, model group, akebia saponin D 150 mg / kg / d group and metformin group were placed in the cages of the clams energy metabolism monitoring system. After the mice adapted for 24 hours, the oxygen consumption (VO 2 ), exhaled carbon dioxide (VCO 2 ) and energy expenditure, with adequate water and feed, 12 h light and 12 h dark cycle, and body weight as an indicator of VO 2 、VCO 2 and energy consumption.

[0084] Experimental results: Combination Figures 12 to 17 As shown, it can be seen that Akebia saponin D can enhance the energy metabolism rate and promote thermogenesis in mice fed a high-fat diet.

[0085] Based on the above Examples 1 to 7, Akebia saponin D reduces the size of white adipocytes (Example 2), improves the insulin resistance induced by high fat (Example 3), and Akebia saponin D changes the expression levels of UCP1 mRNA and UCP1 protein in adipocytes and the changes of many thermogenic genes (Examples 4 and 5). In summary, it can be seen that Akebia saponin D can promote the beigeization of subcutaneous white fat and the activation of brown fat, and promote the heat production capacity of fat (Examples 6 and 7), thereby preventing and treating high-fat diet obesity (Example 1).

[0086] Example 8 Animal experiment drug preparation method.

[0087] Table 1 is the preparation method of Akebia saponin D. Table 2 is the preparation method of Metformin. Wherein, W = drug weight / (drug weight+normal saline weight), 1 ml normal saline weight = 1030 mg.

[0088] Table 1

[0089]

[0090] Table 2

[0091]

[0092] The above description is only a preferred embodiment of the present invention and does not limit the present invention in any form. Any simple modification, equivalent changes and modifications made to the above embodiments based on the technical essence of the present invention are still within the protection scope of the technical solution of the present invention.

Claims

1. A drug for preventing and treating obesity, Features: The invention is composed of akebia saponin D and pharmaceutical excipients. The mass percentage of akebia saponin D is 0.54% to 2.83%, and the purity of akebia saponin D is greater than or equal to 98%.

2. The drug for preventing and treating obesity according to claim 1, Features: The dosage of the akebia saponin D is 37.5-150 mg / kg / d.

3. The drug for preventing and treating obesity according to claim 2, Features: The preparations used are oral liquid, powder, granules, tablets, capsules, drop pills, pills or syrups.

4. The drug for preventing and treating obesity according to claim 3, Features: The pharmaceutical excipient is selected from any one of the following: freeze-dried powder excipient, oral preparation excipient.

5. Use of the drug for preventing and treating obesity according to claim 4, Features: The medicine is used for high-fat diet obesity.

6. Use of the drug for preventing and treating obesity according to claim 4, Features: The drug is used to reduce the size, volume, and weight of white fat cells.

7. Use of the drug for preventing and treating obesity according to claim 4, Features: The drug is used for improving the insulin resistance state induced by a high-fat diet.

8. Use of the drug for preventing and treating obesity according to claim 4, Features: The drug is used for changing the expression level of UCP1 mRNA of the white fat beige gene in fat cells and promoting the expression of UCP1 in brown fat tissue.

9. Use of the drug for preventing and treating obesity according to claim 4, Features: The drug is used to promote beigeization of subcutaneous white fat and activation of brown fat, promote the expression of heat-related genes, increase the heat-generating capacity of fat cells, relieve insulin resistance, increase the utilization of blood sugar and blood lipids, and reduce lipid accumulation in adipose tissue.

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