Lactobacillus plantarum strain and composition containing same for preventing or treating metabolic diseases

Abstract

The present invention relates to a novel plant lactobacillus strain and a composition for preventing or treating metabolic diseases comprising the strain. According to the plant lactobacillus strain (preservation number KCTC 14107BP) of the present invention, fat accumulation in white adipose tissue, brown adipose tissue and liver tissue can be effectively inhibited. The plant lactobacillus strain shows an excellent blood sugar improvement effect, particularly can reduce fasting blood sugar level. The plant lactobacillus strain can improve glucose tolerance and increase insulin sensitivity, thereby effectively improving insulin resistance. In addition, the plant lactobacillus strain can control the concentration of metabolic hormones in the blood. Therefore, the plant lactobacillus strain can be usefully used to prevent or treat metabolic diseases.

Description

Technical Field

[0001] The present disclosure relates to a novel Lactobacillus Plantarum strain and a composition comprising the strain for preventing or treating metabolic diseases. Background Art

[0002] As society develops, obesity has become a serious disease, and the World Health Organization (WHO) has recognized obesity as a disease that requires treatment. Recently, a trend of increasing obesity prevalence due to a Westernized diet has also been observed in Korea, and interest in the treatment and prevention of obesity has been growing. Obesity refers to a state of excessive accumulation of body fat due to an imbalance between food consumption and energy expenditure. In addition, obesity is closely related to insulin resistance, glucose tolerance, hyperlipidemia, etc., and may be accompanied by metabolic diseases including cardiovascular disease, fatty liver disease, cancer, and diabetes as complications.

[0003] Recently, it has been known that inflammatory responses are increased in adipose tissue in obese patients, and obesity is sometimes considered a form of low-grade systemic inflammation. In particular, inflammatory macrophages, which increase in proportion to the size of adipose tissue, have been reported to increase inflammatory responses, and inflammatory adipokines produced and secreted by adipose tissue in this state are pathogenic factors for metabolic diseases such as cardiovascular disease and diabetes. Therefore, obesity, which increases these molecules, can be regarded as the cause of almost all adult diseases.

[0004] The obesity drugs currently prescribed include Xenical (Roche Pharmaceuticals., Switzerland), Reductil (Abbott Co., the U.S.) and Exolise (Arkopharma LLC, France) etc. Obesity drugs are mainly divided into appetite suppressants, energy consumption promoters or fat absorption inhibitors, and most obesity drugs are appetite suppressants, which suppress appetite by controlling neurotransmitters associated with the hypothalamus. However, conventional obesity drugs have side effects such as heart disease, respiratory diseases and nervous system diseases, and have the problem of low persistence in vivo. Therefore, it is necessary to develop safe and effective obesity drugs.

[0005] Meanwhile, probiotics using safe microorganisms such as lactic acid bacteria to prevent or treat obesity have been actively studied. In particular, studies have shown that lactic acid bacteria have effects such as maintaining normal intestinal flora, improving intestinal flora, anti-diabetic and anti-lipid effects, inhibiting carcinogenesis, inhibiting colon cancer, and nonspecific activity of the host immune system.

[0006] Regarding lactic acid bacteria associated with obesity prevention and treatment effects, Korean Patent No. 10-1494279 discloses Lactobacillus plantarum KY1032 strain (deposit number KCCM-10430) having an inhibitory effect on adipocyte differentiation, Korean Patent No. 10-0996577 discloses Lactobacillus curvatus HY7601 (deposit number KCTC 11456BP) having an obesity inhibitory effect, and Korean Patent No. 10-1394348 discloses Lactobacillus plantarum DSR920 strain (deposit number KCCM 11210P) having an inhibitory effect on adipocyte differentiation, but none of them have matured enough to achieve commercial success.

[0007] Therefore, there is a need to continue researching new strains with excellent anti-obesity effects. Summary of the invention

[0008] Technical issues

[0009] Therefore, the present inventors have studied and developed new strains having excellent anti-obesity effects, and found that the Lactobacillus plantarum strain (Accession No. KCTC 14107BP) exhibits excellent anti-obesity effects, thereby completing the present invention.

[0010] Solution

[0011] One aspect of the present invention provides a Lactobacillus plantarum strain (deposit number KCTC 14107BP).

[0012] Another aspect of the present invention provides a pharmaceutical composition for preventing or treating metabolic diseases, the pharmaceutical composition comprising Lactobacillus plantarum strain (deposit number KCTC 14107BP) or a culture thereof as an active ingredient.

[0013] Another aspect of the present invention provides a food composition comprising a Lactobacillus plantarum strain (deposit number KCTC 14107BP) or a culture thereof.

[0014] Another aspect of the present invention provides a feed composition, comprising a Lactobacillus plantarum strain (Deposit No. KCTC 14107BP) or a culture thereof.

[0015] Still another aspect of the present invention provides a method for preventing or treating metabolic diseases comprising the Lactobacillus plantarum strain (Deposit No. KCTC 14107BP) or a culture thereof.

[0016] Effects of the Invention

[0017] The present disclosure relates to a plant lactobacillus strain and a composition for preventing or treating metabolic diseases comprising the strain. According to the plant lactobacillus strain of the present invention (preservation number KCTC 14107BP), fat accumulation in white adipose tissue, brown adipose tissue and liver tissue can be effectively inhibited. The plant lactobacillus strain can show excellent blood sugar improvement effects, particularly can reduce fasting blood sugar levels. The plant lactobacillus strain can effectively improve insulin resistance by improving glucose tolerance and increasing insulin sensitivity. In addition, the plant lactobacillus strain can regulate the concentration of metabolic hormones in the blood. Therefore, the plant lactobacillus strain can be usefully used to prevent or treat metabolic diseases. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] The exemplary embodiments may be understood in more detail through the following description in conjunction with the accompanying drawings, in which:

[0019] Figures 1 to 3 It is a graph showing the body weight of mice fed a high-fat diet after oral administration of 16 lactic acid bacteria strains, respectively, compared with mice fed a high-fat diet alone.

[0020] Figure 4 The graph compares the sizes of fat cells in white adipose tissue from mice fed a normal diet, mice fed a high-fat diet, mice fed a high-fat diet and orally administered with common lactic acid bacteria, and mice fed a high-fat diet and orally administered with Lactobacillus plantarum (L. Plantarum) GB104 strain.

[0021] Figure 5 The graph compares the sizes of fat cells in brown adipose tissue of mice fed a normal diet, mice fed a high-fat diet, mice fed a high-fat diet and orally administered with common lactic acid bacteria, and mice fed a high-fat diet and orally administered with Lactobacillus plantarum GB104 strain.

[0022] Figure 6 The graph compares the liver weights of mice fed a normal diet, mice fed a high-fat diet, mice fed a high-fat diet and orally administered with common lactic acid bacteria, and mice fed a high-fat diet and orally administered with the Lactobacillus plantarum GB104 strain.

[0023] Figure 7 The graph compares the degree of fat accumulation in liver tissue of mice fed a normal diet, mice fed a high-fat diet, mice fed a high-fat diet and orally administered with common lactic acid bacteria, and mice fed a high-fat diet and orally administered with Lactobacillus plantarum GB104 strain.

[0024] Figure 8The graph compares the fasting blood glucose levels of mice fed a normal diet, mice fed a high-fat diet, mice fed a high-fat diet and orally administered with common lactic acid bacteria, and mice fed a high-fat diet and orally administered with Lactobacillus plantarum GB104 strain to confirm the blood glucose lowering effect.

[0025] Fig. 9 This graph compares blood sugar levels over time after administration of glucose in mice fed a normal chow, mice fed a high-fat diet, mice fed a high-fat diet and orally administered with common lactic acid bacteria, and mice fed a high-fat diet and orally administered with Lactobacillus plantarum GB104 strain to confirm the glucose tolerance-improving effect.

[0026] Fig.10 is a graph comparing blood sugar levels over time after administration of insulin in mice fed a normal chow, mice fed a high-fat diet, mice fed a high-fat diet and orally administered with common lactic acid bacteria, and mice fed a high-fat diet and orally administered with Lactobacillus plantarum GB104 strain to confirm the insulin resistance improving effect; and

[0027] Fig.11 This graph compares the concentration of glucagon-like peptide-1 (GLP-1) in the blood of mice fed a normal diet, mice fed a high-fat diet, mice fed a high-fat diet and orally administered with common lactic acid bacteria, and mice fed a high-fat diet and orally administered with Lactobacillus plantarum GB104 strain to confirm the ability to regulate metabolic hormones. DETAILED DESCRIPTION

[0028] One aspect of the present invention provides a Lactobacillus plantarum strain (deposit number KCTC 14107BP).

[0029] Lactobacillus is an aerobic or facultative anaerobic Gram-positive rod widely distributed in nature. The genus Lactobacillus includes Lactobacillus plantarum, Lactobacillus sakei, etc. The inventors selected a new strain of Lactobacillus plantarum with excellent anti-obesity effect and named it "Lactobacillus plantarum GB104". The strain was deposited in the Korea Collection for Type Cultures, Korea Research Institute of Bioscience and Biotechnology, Korea Research Institute of Bioscience and Biotechnology on September 6, 2019 with the deposit number SD1337. The same strain was deposited in the Korea Collection for Type Cultures, Korea Research Institute of Bioscience and Biotechnology, Korea Research Institute of Bioscience and Biotechnology on January 14, 2020 with the deposit number KCTC 14107BP. In addition, the strain belongs to a probiotic strain, is harmless to the human body, and can be used without side effects.

[0030] As used herein, the term "Lactobacillus Plantarum GB104" may be interchangeably described as Lactobacillus Plantarum GB104 or Lactobacillus Plantarum strain (Deposit No. KCTC 14107BP).

[0031] Another aspect of the present invention provides a pharmaceutical composition for preventing or treating metabolic diseases, the pharmaceutical composition comprising Lactobacillus plantarum strain (deposit number KCTC 14107BP) or a culture thereof as an active ingredient.

[0032] Plant lactobacillus strain (preserving number KCTC 14107BP) is the same as above. In this case, the strain can be alive or dead, and preferably live strain. In addition, the culture of the strain may contain or may not contain the strain, preferably contains the strain.

[0033] Based on the total weight of the composition, the composition includes a therapeutically effective amount or a nutritionally effective concentration of an active ingredient, Lactobacillus plantarum strain (preservation number KCTC 14107BP) or a culture thereof, wherein the content of the active ingredient is 10 4 Up to 10 16 CFU / g, preferably 10 6 Up to 10 12 CFU / g, or including cultures with an equivalent amount of live strains. Generally speaking, for adult patients, 1×10 6 CFU / g or more of live strains, preferably 1×10 8 Up to 1×10 12 CFU / g of live strains.

[0034] As used herein, the term "metabolic disease", also referred to as metabolic syndrome, is a disease believed to be caused by insulin resistance and is a symptom of two or more abnormalities in cholesterol, blood pressure and blood sugar levels. Metabolic syndrome is a conceptualization of the phenomenon that the risk factors for various cardiovascular diseases and type 2 diabetes are clustered together as a disease group, and encompasses insulin resistance and all the complex and diverse metabolic abnormalities and clinical features associated with insulin resistance. Specifically, a metabolic disease can be any one selected from the group consisting of obesity, hypertension, arteriosclerosis, hyperlipidemia, fatty liver, nonalcoholic fatty liver disease, hyperinsulinemia, diabetes and insulin resistance syndrome.

[0035] As used herein, the term "obesity", also referred to as polyadiposity, is a disease in which excessive body fat is abnormally accumulated. Irregular eating habits, excessive food intake, lack of physical activity, endocrine system diseases, genetic factors, psychological factors, medication, etc. can all lead to obesity. In addition, obesity can increase the incidence of arteriosclerosis, cardiovascular disease (stroke and ischemic cardiovascular disease), hypertension, diabetes, hyperlipidemia, fatty liver, cholelithiasis, obstructive sleep apnea, menstrual disorders, polycystic ovarian disease, infertility, loss of libido, depression, degenerative arthritis, gout, etc. Obesity can be simple obesity, symptomatic obesity, childhood obesity, adult obesity, cell proliferation obesity, cell hypertrophy obesity, upper body obesity, lower body obesity, visceral fat obesity or subcutaneous fat obesity.

[0036] As used herein, the term "hypertension" refers to the phenomenon of increased perfusion blood pressure of blood flowing through arteries. If the systolic blood pressure reaches 140 mmHg and the diastolic blood pressure reaches above 90 mmHg, it can generally be diagnosed as hypertension. Hypertension has no obvious symptoms. There are primary (or idiopathic) hypertension of unknown cause, and secondary hypertension caused by kidney disease, endocrine disease, pregnancy poisoning, etc. Most cases of hypertension (90% to 95%) are primary hypertension, which is believed to be caused by genetic reasons as well as environmental factors (such as obesity, stress, alcohol and smoking).

[0037] As used herein, the term "atherosclerosis" is defined as a phenomenon in which the width of the arterial wall becomes narrower due to loss of elasticity of the arterial wall, abnormal tissue proliferation, and accumulation of fat in the inner layer of the arterial wall. Arteriosclerosis is a term for arterial lesions and is named according to the organ affected by arteriosclerosis. For example, arteriosclerosis includes, but is not limited to, cerebral infarction caused by arteriosclerosis and myocardial infarction caused by coronary artery sclerosis.

[0038] As used herein, the term "hyperlipidemia" is a disease caused by a large amount of lipids (such as triglycerides and cholesterol) in the blood due to the inability of lipid metabolism to proceed normally. Specifically, hyperlipidemia refers to a state in which lipid components (such as triglycerides, LDL cholesterol and free fatty acids) in the blood increase. Hyperlipidemia includes, but is not limited to, hypercholesterolemia or hypertriglyceridemia.

[0039] As used herein, the term "fatty liver" is a state in which fat is excessively accumulated in liver cells due to lipid metabolism disorder, and is defined as a condition in which fat reaches 5% or more of the liver weight. This causes various diseases, such as angina pectoris, myocardial infarction, stroke, arteriosclerosis, fatty liver, pancreatitis, etc. Fatty liver is divided into alcoholic fatty liver caused by drinking and non-alcoholic fatty liver disease (NAFLD) which is not caused by alcohol.

[0040] As used herein, the term "non-alcoholic fatty liver disease" refers to a condition in which fatty liver is not caused by alcohol, and includes a range of liver damage processes, from simple fatty degeneration of the liver, non-alcoholic steatohepatitis (NASH) to cirrhosis. The causes of non-alcoholic fatty liver disease are: side effects of drugs such as antiarrhythmic agents, antiviral agents, steroids, or cytotoxic agents; excessive calorie consumption such as carbohydrates; obesity; diabetes; and some genetic causes.

[0041] As used herein, the term "diabetes" is a chronic disease characterized by a relative or absolute lack of insulin leading to glucose intolerance. Diabetes includes all types of diabetes, such as type 1 diabetes, type 2 diabetes and hereditary diabetes, but is not limited thereto. Type 1 diabetes is insulin-dependent diabetes, mainly caused by β-cell destruction. As used herein, the term "type 2 diabetes" is insulin-independent diabetes, which is caused by insulin resistance. Type 2 diabetes is caused by the fact that no increase in insulin is detected in muscle and adipose tissue, or even if insulin is detected, it does not act effectively.

[0042] As used herein, the term "insulin resistance" refers to a state in which cells do not respond to insulin, which lowers blood sugar levels, and therefore cannot burn glucose efficiently. When insulin resistance is high, the body thinks more insulin is needed and produces more insulin. This can lead to hyperinsulinemia, high blood pressure or dyslipidemia, as well as heart disease and diabetes.

[0043] As used herein, the term "insulin resistance syndrome" is a general term for diseases caused by insulin resistance. It is characterized by cellular resistance to the action of insulin, hyperinsulinemia and elevated very low-density lipoprotein (VLDL) and triglycerides, as well as decreased high-density lipoprotein (HDL), hypertension, etc., and is recognized as a risk factor for cardiovascular disease and type 2 diabetes.

[0044] According to an embodiment of the present invention, the strain can inhibit fat accumulation in white adipose tissue. Specifically, in an embodiment of the present invention, oral administration of the strain to a mouse model fed a high-fat diet resulted in a significant decrease in the size of fat cells in the white adipose tissue of the mouse model. At the same time, when common lactic acid bacteria were orally administered to a mouse model fed a high-fat diet, the size of fat cells in the white adipose tissue of the mouse model did not decrease. Based on this, it was confirmed that the strain inhibited fat accumulation in white adipose tissue ( Figure 4 ).

[0045] According to an embodiment of the present invention, the strain can inhibit fat accumulation in brown adipose tissue. Specifically, in an embodiment of the present invention, oral administration of the strain to a mouse model fed a high-fat diet resulted in a significant reduction in the size of fat cells in the brown adipose tissue of the mouse model. At the same time, when common lactic acid bacteria were orally administered to a mouse model fed a high-fat diet, the size of fat cells in the brown adipose tissue of the mouse model did not decrease. Based on this, it is confirmed that the strain inhibits fat accumulation in brown adipose tissue ( Figure 5 ).

[0046] According to an embodiment of the present invention, the strain can reduce liver weight and inhibit fat accumulation in liver tissue. Specifically, in an embodiment of the present invention, oral administration of the strain to a mouse model fed a high-fat diet resulted in a reduction in liver weight and fat accumulation in the mouse model's tissue. At the same time, when common lactic acid bacteria were orally administered to a mouse model fed a high-fat diet, a large amount of fat accumulated in the mouse model's liver tissue, and there was no change in body weight. Based on this, it was confirmed that the strain reduced liver weight and inhibited fat accumulation in tissue ( Figure 6 and Figure 7 ).

[0047] According to an embodiment of the present invention, the strain can reduce blood sugar levels. Preferably, the strain can reduce fasting blood sugar levels and improve glucose tolerance. Specifically, in an embodiment of the present invention, oral administration of the strain to a mouse model fed a high-fat diet results in a reduction in the fasting blood sugar level and the blood sugar level after administration of glucose in the mouse model. At the same time, when common lactic acid bacteria were orally administered to a mouse model fed a high-fat diet, neither the fasting blood sugar level nor the blood sugar level after administration of glucose was reduced. Based on this, it is confirmed that the strain reduces fasting blood sugar levels and improves glucose tolerance ( Figure 8 and Fig. 9 ).

[0048] According to an embodiment of the present invention, the strain can improve insulin resistance. Specifically, in an embodiment of the present invention, when the strain is orally administered to a mouse model fed a high-fat diet, the blood sugar level of the mouse model is significantly reduced after insulin administration. At the same time, when common lactic acid bacteria are orally administered to a mouse model fed a high-fat diet, the blood sugar level after insulin administration does not decrease. Based on this, it is confirmed that the strain improves insulin resistance by increasing insulin sensitivity ( Fig.10 ).

[0049] According to an embodiment of the present invention, the strain can regulate the secretion of the metabolic hormone GLP-1.

[0050] As used herein, the term "metabolic hormone" refers to a hormone involved in metabolic regulation, and may preferably be an incretin. As used herein, the term "incretin" is a hormone secreted in the gastrointestinal tract due to nutrients in food after eating, and is used to promote insulin secretion in the pancreas in a blood glucose-dependent manner. Incretins include GLP-1 and glucose-dependent insulinotropic peptide (GIP). "GLP-1" acts on the pancreas to increase insulin secretion and reduce glucagon secretion, thereby exhibiting a hypoglycemic effect. In addition, GLP-1 delays gastric emptying, suppresses appetite, and improves β-cell function to exhibit anti-diabetic and anti-obesity effects.

[0051] In an embodiment of the present invention, oral administration of the strain to a mouse model fed a high-fat diet resulted in an increase in the concentration of blood GLP-1, which was reduced in the mouse model. However, when common lactic acid bacteria were orally administered, no change in the concentration of GLP-1 in the blood was observed. Based on this, it was confirmed that the strain regulates the concentration of GLP-1 in the blood ( Fig.11 ).

[0052] The composition may further comprise a cryoprotectant or excipient. Specifically, the cryoprotectant may be one or more selected from the group consisting of glycerol, trehalose, maltodextrin, skimmed milk powder and starch. In addition, the excipient may be one or more selected from the group consisting of glucose, dextrin and skimmed milk powder.

[0053] Based on the gross weight of the composition, the composition can include 0.01wt% to 20wt% or 0.01wt% to 10wt% of a cryoprotectant, specifically, the composition can include 5wt% to 20wt% of glycerol, 2wt% to 10wt% of trehalose, 2wt% to 10wt% of maltodextrin, 0.5wt% to 2wt% of skim milk powder and 0.1wt% to 1wt% of starch. In addition, based on the gross weight of the composition, the composition can include 75wt% to 95wt% or 85wt% to 95wt% of an excipient.

[0054] Another aspect of the present invention provides a food composition comprising a Lactobacillus plantarum strain (deposit number KCTC 14107BP) or a culture thereof.

[0055] The Lactobacillus plantarum strain (Accession No. KCTC 14107BP) is the same as that described above.

[0056] The food composition includes all forms, such as functional food, nutritional supplement, health food, food additives, and the types of food compositions can be prepared into various forms according to conventional methods known in the art.

[0057] In the case where the strain is used as a food additive, the strain can be added as it is, or can be used together with other foods or food ingredients, and can be used appropriately according to conventional methods. The mixing amount of the active ingredient can be appropriately determined according to the purpose of use. Usually, when preparing food or beverages, the addition amount of the active ingredient in the raw material composition containing the strain can be 0.0001wt% to 1wt%, particularly 0.001wt% to 0.1wt%.

[0058] Another aspect of the present invention provides a feed composition, comprising a Lactobacillus plantarum strain (Deposit No. KCTC 14107BP) or a culture thereof.

[0059] The Lactobacillus plantarum strain (Accession No. KCTC 14107BP) is the same as that described above.

[0060] The feed composition can be prepared according to various methods for preparing feed compositions known in the art by adding Lactobacillus plantarum strain (Deposit No. KCTC 14107BP) in an appropriate effective concentration range.

[0061] Still another aspect of the present invention provides a method for preventing and treating metabolic diseases, the method comprising administering a Lactobacillus plantarum strain (Deposit No. KCTC 14107BP) or a culture thereof to a subject.

[0062] The object may suffer from metabolic diseases. In addition, the object may be a mammal, preferably a human. In this case, the plant lactobacillus strain (preserving number KCTC 14107BP) is the same as described above. In addition, the route of administration, dosage and frequency of administration of the strain or its culture may be administered to the object in various ways and amounts according to the patient's condition and the presence or absence of side effects, and the best method of administration, dosage and frequency of administration may be suitably selected by those skilled in the art in an appropriate range. In addition, the type of metabolic diseases is as described above.

[0063] Another aspect of the present invention provides use of a Lactobacillus plantarum strain (deposit number KCTC 14107BP) or a culture thereof for treating metabolic diseases.

[0064] In this case, the Lactobacillus plantarum strain (Accession No. KCTC 14107BP) is the same as that described above. In addition, the types of metabolic diseases are as described above. DETAILED DESCRIPTION

[0066] The present invention will be described in more detail below by the following examples. However, the following examples are only used to illustrate the present invention, and the scope of the present invention is not limited by the following examples.

[0067] Example 1. Screening of strains with anti-obesity effects

[0068] A mouse model was used to select lactic acid bacteria with anti-obesity effects from 16 lactic acid bacteria purchased from Mediogen Co., Specifically, C57BL / 6 fed with a 60% high fat diet (HFD) and then orally administered with each lactic acid bacteria were used as the experimental group. Mice fed only with a 60% high fat diet were used as the control group. In this case, each mouse was fed 5×10 9 Each lactic acid bacteria was orally administered by CFU. The anti-obesity effect was determined based on the difference in body weight between the experimental group and the control group.

[0069] As a result, the strain Lactobacillus plantarum GB104 was the most effective in suppressing weight gain. In this case, some Lactobacillus plantarum lactic acid bacteria did not show anti-obesity effects ( Figures 1 to 3 ). Based on this, it was confirmed that the Lactobacillus plantarum GB104 strain exhibited anti-obesity effects among Lactobacillus plantarum lactic acid bacteria.

[0070] Example 2. Confirmation of the fat accumulation inhibitory effect of Lactobacillus plantarum GB104 strain in white adipose tissue

[0071] A mouse model was used to confirm the fat accumulation inhibitory effect of Lactobacillus plantarum GB104 (Accession No. KCTC 14107BP) strain in white adipose tissue. Specifically, C57BL / 6 mice fed with a 60% high-fat diet (HFD) and then orally administered with Lactobacillus plantarum GB104 strain were used as the experimental group. In addition, mice fed only with a 60% high-fat diet were used as a negative control group, and mice fed with a 60% high-fat diet and orally administered with common lactic acid bacteria (Lactobacillus plantarum MG5120) were used as a positive control group. In addition, mice fed a normal chow diet (NCD) were used as a normal group. In this case, each mouse was fed 5×10 9 CFU were orally administered with common lactic acid bacteria purchased from Mediogen Co., or Lactobacillus plantarum GB104 strain.

[0072] After the administration of each test substance was completed, white adipose tissue was isolated by autopsy. The isolated white adipose tissue was fixed with 10% neutral buffered formalin. Then, paraffin sections were prepared, stained with hematoxylin and eosin (H&E), and then the cell size was observed.

[0073] The results showed that the adipocyte size of the negative control group and the positive control group fed with a high-fat diet increased compared with the normal group, while the adipocyte size of the experimental group orally administered with the Lactobacillus plantarum GB104 strain was significantly reduced ( Figure 4 ). Based on this, it was confirmed that the Lactobacillus plantarum GB104 strain effectively inhibits fat accumulation in white adipose tissue.

[0074] Example 3. Confirmation of the inhibitory effect of Lactobacillus plantarum GB104 strain on fat accumulation in brown adipose tissue

[0075] A mouse model was used to confirm the fat accumulation inhibitory effect of Lactobacillus plantarum GB104 strain in brown adipose tissue. Specifically, C57BL / 6 mice fed with 60% (HFD) and then orally administered with Lactobacillus plantarum GB104 strain were used as the experimental group. In addition, mice fed only with a 60% high-fat diet were used as a negative control group, and mice fed a 60% high-fat diet and orally administered with common lactic acid bacteria (Lactobacillus plantarum MG5120) were used as a positive control group. In addition, mice fed a normal diet (NCD) were used as a normal group. In this case, each mouse was fed 5×10 9 CFU were orally administered with common lactic acid bacteria purchased from Mediogen Co., or Lactobacillus plantarum GB104 strain.

[0076] After the administration of each test substance was completed, brown adipose tissue was isolated from each group of mice by necropsy. The isolated brown adipose tissue was fixed with 10% neutral buffered formalin. Then, paraffin sections were prepared, stained with H&E, and then the cell size was observed.

[0077] The results showed that the adipocyte size of the negative control group and the positive control group mice fed with a high-fat diet increased compared with the normal group, while the adipocyte size of the experimental group orally administered with the Lactobacillus plantarum GB104 strain was significantly reduced ( Figure 5 ). Based on this, it was confirmed that the Lactobacillus plantarum GB104 strain effectively inhibits fat accumulation in brown adipose tissue.

[0078] Example 4. Confirmation of the inhibitory effect of Lactobacillus plantarum GB104 strain on fat accumulation in liver tissue

[0079] A mouse model was used to confirm the fat accumulation inhibitory effect of Lactobacillus plantarum GB104 strain in liver tissue. Specifically, C57BL / 6 mice fed with 60% (HFD) and then orally administered with Lactobacillus plantarum GB104 strain were used as the experimental group. In addition, mice fed only with a 60% high-fat diet were used as a negative control group, and mice fed a 60% high-fat diet and orally administered with common lactic acid bacteria (Lactobacillus plantarum MG5120) were used as a positive control group. In addition, mice fed a normal diet (NCD) were used as a normal group. In this case, each mouse was fed 5×10 9 CFU were orally administered with common lactic acid bacteria purchased from Mediogen Co., or Lactobacillus plantarum GB104 strain.

[0080] After administration of each test substance, the liver was removed by autopsy and weighed, and the weights of the groups were compared and evaluated. The extracted liver was fixed with 10% buffered formalin, paraffin sections were prepared, stained with H&E, and the cell size was observed.

[0081] The results showed that the liver weight of the negative control group and the positive control group mice fed with a high-fat diet increased compared with the normal group, while the liver weight of the experimental group mice orally administered with the Lactobacillus plantarum GB104 strain was significantly reduced compared with the negative control group ( Figure 6 ). In addition, compared with the normal group, the fat accumulation in the liver tissue of the negative and positive control group mice fed with a high-fat diet increased, while the fat accumulation in the liver tissue of the experimental group mice orally administered with the Lactobacillus plantarum GB104 strain was very small and the fat accumulation level was similar to that of the normal group ( Figure 7 ). Based on this, it was confirmed that the Lactobacillus plantarum GB104 strain effectively inhibited liver weight and fat accumulation in liver tissue.

[0082] Example 5. Confirmation of the fasting blood sugar lowering and glucose tolerance improving effects of Lactobacillus plantarum GB104 strain

[0083] A glucose tolerance test (GTT) was performed to confirm the glucose tolerance improving effect of Lactobacillus plantarum GB104 strain. First, C57BL / 6 mice fed with 60% (HFD) and then orally administered with Lactobacillus plantarum GB104 strain were used as the experimental group. In addition, mice fed only with a 60% high-fat diet were used as a negative control group, and mice fed with a 60% high-fat diet and orally administered with common lactic acid bacteria (Lactobacillus plantarum MG5120) were used as a positive control group. In addition, mice fed a normal diet (NCD) were used as a normal group. In this case, each mouse was fed 5×10 9 CFU were orally administered with common lactic acid bacteria purchased from Mediogen Co., or Lactobacillus plantarum GB104 strain.

[0084] For the glucose tolerance test, mice were fasted for 16 hours or longer, and then a glucose solution was injected intraperitoneally at a dose of 1 g / kg. Then, blood was collected from the tail vein of the mice after 0, 30, 60, 90, and 120 minutes, and blood glucose was measured using a glucometer. In this case, blood glucose at 0 minutes refers to fasting blood glucose.

[0085] The results showed that the fasting blood glucose levels of the negative and positive control mice fed a high-fat diet increased significantly compared with the normal group. At the same time, the fasting blood glucose levels of the experimental group mice orally administered with the Lactobacillus plantarum GB104 strain were significantly reduced compared with the negative control group ( Figure 8 ).

[0086] In addition, it was confirmed that after the administration of glucose, the blood glucose levels of the negative and positive control group mice fed a high-fat diet were higher than those of the normal group, while the blood glucose levels of the experimental group mice orally administered with the Lactobacillus plantarum GB104 strain were significantly lower than those of the negative control group ( Fig. 9 ). Based on this, it was confirmed that the Lactobacillus plantarum GB104 strain showed fasting blood sugar lowering and glucose tolerance improving effects.

[0087] Example 6. Confirmation of the insulin resistance-improving effect of Lactobacillus plantarum GB104 strain

[0088] An insulin tolerance test (ITT) was performed to confirm the insulin resistance improving effect of Lactobacillus plantarum GB104 strain. First, C57BL / 6 mice fed with 60% (HFD) and then orally administered with Lactobacillus plantarum GB104 strain were used as the experimental group. In addition, mice fed only with a 60% high-fat diet were used as a negative control group, and mice fed with a 60% high-fat diet and orally administered with common lactic acid bacteria (Lactobacillus plantarum MG5120) were used as a positive control group. In addition, mice fed a normal diet (NCD) were used as a normal group. In this case, each mouse was fed 5×10 9 CFU were orally administered with common lactic acid bacteria purchased from Mediogen Co., or Lactobacillus plantarum GB104 strain.

[0089] For the insulin tolerance test, mice were fasted for 4.5 hours and then insulin solution was intraperitoneally administered at a dose of 1 U / kg. Blood was collected from the tail vein of the mice after 0, 30, 60, 90 and 120 minutes, and blood glucose was measured using a glucometer.

[0090] The results confirmed that after the administration of insulin, the blood glucose levels of the negative and positive control mice fed a high-fat diet were higher than those of the normal group, while the blood glucose levels of the experimental group mice orally administered with the Lactobacillus plantarum GB104 strain were significantly lower than those of the negative control group ( Fig.10 ). Based on this, it was confirmed that the Lactobacillus plantarum GB104 strain effectively improved insulin resistance by increasing insulin sensitivity.

[0091] Example 7. Confirmation of the GLP-1 secretion-promoting effect of Lactobacillus plantarum GB104 strain

[0092] A mouse model was used to confirm the GLP-1 regulatory effect caused by the administration of Lactobacillus plantarum GB104 strain. Specifically, C57BL / 6 mice fed with 60% (HFD) and then orally administered with Lactobacillus plantarum GB104 strain were used as the experimental group. In addition, mice fed only with a 60% high-fat diet were used as a negative control group, and mice fed a 60% high-fat diet and orally administered with common lactic acid bacteria (Lactobacillus plantarum MG5120) were used as a positive control group. In addition, mice fed a normal diet (NCD) were used as a normal group. In this case, each mouse was fed 5×10 9 CFU were orally administered with common lactic acid bacteria purchased from Mediogen Co., or Lactobacillus plantarum GB104 strain.

[0093] Serum was separated from the blood of each group of mice, and the concentration of GLP-1 in the serum was analyzed using the Bio-plexPro Mouse Diabetes 8-plex Detection Kit (Bio-rad, Hercules, CA, USA). The sample analysis procedure was carried out according to the protocol in the kit.

[0094] The results showed that the concentration of GLP-1 in the serum of the negative and positive control mice fed with a high-fat diet was lower than or similar to that of the normal group, while the concentration of GLP-1 in the experimental group of mice orally administered with the Lactobacillus plantarum GB104 strain was significantly higher than that of the negative control group ( Fig.11 ). Based on this, the effect of Lactobacillus plantarum GB104 strain in increasing the concentration of GLP-1 in serum was confirmed.

[0095] <Accession Number>

[0096] Name of depository institution: Korea Center for Typical Culture Collection (KCTC), Korea Institute of Biotechnology

[0097] Accession number: KCTC14107BP

[0098] Date of preservation: 20200114.

Claims

1. A Lactobacillus Plantarum strain with a deposit number of KCTC 14107BP.

2. A pharmaceutical composition for preventing or treating metabolic diseases, comprising a Lactobacillus plantarum strain with a preservation number of KCTC14107BP or a culture thereof as an active ingredient.

3. The pharmaceutical composition for preventing or treating metabolic diseases according to claim 2, wherein: The metabolic disease is selected from the group consisting of hypertension, arteriosclerosis, hyperlipidemia, non-alcoholic fatty liver disease, hyperinsulinemia, type 2 diabetes and insulin resistance syndrome.

4. The pharmaceutical composition for preventing or treating metabolic diseases according to claim 2, wherein: The strain inhibits fat accumulation in white adipose tissue.

5. The pharmaceutical composition for preventing or treating metabolic diseases according to claim 2, wherein: The strain reduces fat accumulation in brown adipose tissue.

6. The pharmaceutical composition for preventing or treating metabolic diseases according to claim 2, wherein: The strain inhibits fat accumulation in liver tissue.

7. The pharmaceutical composition for preventing or treating metabolic diseases according to claim 2, wherein: The strain reduces blood sugar levels.

8. The pharmaceutical composition for preventing or treating metabolic diseases according to claim 2, wherein: The strain reduces insulin resistance.

9. The pharmaceutical composition for preventing or treating metabolic diseases according to claim 2, wherein: The strain regulates the concentration of metabolic hormones in the blood.

10. The pharmaceutical composition for preventing or treating metabolic diseases according to claim 9, wherein: The metabolic hormone is GLP-1.

11. A food composition comprising the Lactobacillus plantarum strain with a preservation number of KCTC 14107BP or a culture thereof.

12. A feed composition comprising the Lactobacillus plantarum strain with a deposit number of KCTC 14107BP or a culture thereof.

13. Use of the Lactobacillus plantarum strain with the deposit number of KCTC 14107BP or its culture in the preparation of a medicament for preventing and treating metabolic diseases, wherein the metabolic diseases are selected from the group consisting of hyperlipidemia, fatty liver disease, diabetes, obesity and insulin resistance syndrome.

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