TW201620533A - Usage of composition containing lactobacillus plantarum in regulating lipid metabolism - Google Patents

Abstract

A usage of composition containing lactobacillus plantarum in regulating lipid metabolism is disclosed, which provides one kind of lactobacillus plantarum that is combined with at least one carbohydrate for a usage of manufacturing a composition to regulate lipid metabolism. By giving an effective quantity of the aforementioned composition to an individual, the cell growth/accumulation of the lipid inside the individual can be prohibited, thereby achieving an efficacy to prevent or treat diseases relating to disorders of lipid metabolism.

Description

Use of a composition containing Lactobacillus plantarum for regulating lipid metabolism

The present invention relates to a second use of a probiotic composition, in particular to the use of a composition comprising Lactobacillus plantarum for regulating lipid metabolism.

According to the changes in modern people's living and eating habits, metabolic syndrome (MetS) such as obesity and diabetes increased year by year. Furthermore, metabolic syndrome is a symptom known to increase risk factors for cardiovascular disease and diabetes, including risk factors such as dyslipidemia, abdominal obesity, and hypertension. One of the main characteristics of metabolic syndrome is insulin resistance, which is caused by visceral obesity, and can determine the development of metabolic syndrome. Although insulin resistance or hyperinsulinemia does not cause obesity, obesity is a physiological variable that increases the likelihood of insulin resistance. According to the World Health Organization's statistical report, 10% of adults worldwide are obese, at least 2.8 million deaths per year can be attributed to being overweight or obese, and 347 million people worldwide suffer from diabetes, estimated at 2030. Diabetes will be the seventh leading cause of death. It can be seen that metabolic syndrome has become a global health concern.

Probiotics are microorganisms that are considered safe and beneficial to the health of the host. Most probiotics are separated by a line out of the gastrointestinal tract, comprising Bifidobacteria (Bifidobacterium), lactic acid bacteria (Lactobacillus), Streptococcus (Streptococcus) and Enterococcus (of Enterococcus) genus and the like, wherein the lactic acid bacteria again presently the most widely applied . For example, Lactobacillus rhamnosus has the effect of reducing intestinal permeability, and can reduce the effect of allergic bowel syndrome in children and the permeability of the intestinal tract against alcoholic hepatitis.

Lactobacillus plantarum (LP) is a Lactobacillus strain characterized by Gram-positive bacteria that is resistant to oxygen and grows at 15 ° C but does not survive at 45 ° C. Current research shows that Lactobacillus plantarum can reduce the risk factors for cardiovascular disease by protecting the atherosclerosis of smokers. Another study pointed out that Lactobacillus plantarum can inhibit the growth of Nocturnal bacteria and improve the efficacy of irritable bowel syndrome. Moreover, Lactobacillus plantarum can reduce the allergic gene marker and has the effect of alleviating allergic symptoms caused by pollen. Recent studies have shown that although Lactobacillus plantarum can regulate the metabolism of sugar, it does not reduce the weight of fat.

As can be seen from the above, the global system is facing a health crisis in which obese people are increasing year by year, and obesity is closely related to hepatic metabolic syndrome, such as fatty liver and type 2 diabetes. Therefore, probiotics have been used to develop an inflammatory response and fat content. The composition, which is capable of improving or preventing the liver-related metabolic syndrome, is an important subject of current researchers.

The main object of the present invention is to provide a use of a composition comprising Lactobacillus plantarum which is capable of effectively regulating lipid metabolism and achieving the effect of preventing or treating diseases associated with abnormal fat metabolism.

In order to achieve the above object, a preferred embodiment of the present invention discloses the use of a Lactobacillus plantarum combined with at least one saccharide for the manufacture of a composition for regulating lipid metabolism. By administering the composition containing an effective amount of Lactobacillus plantarum and a saccharide to a body, the system can inhibit the growth of fat cells and/or the accumulation of fat cells in the body, thereby preventing or treating abnormalities in fat metabolism. The efficacy of related conditions, for example, hepatic metabolic syndrome caused by abnormal lipid metabolism Group, obesity, excessive visceral fat, fatty liver, etc.

Preferably, the Lactobacillus plantarum is Lactobacillus plantarum LP110.

Preferably, the saccharide comprises arabinogalactan and fructooligosaccharide.

In the above embodiment, the composition ratio of the Lactobacillus plantarum to the arabinogalactan is 1:10 to 1:15, and the mass to volume ratio of the Lactobacillus plantarum to the fructooligosaccharide is 50:1 to 150:1, wherein Further, the composition ratio of Lactobacillus plantarum to arabinogalactan is 1:12.5, and the ratio of the mass volume of Lactobacillus plantarum to fructooligosaccharide is preferably 100:1.

Preferably, regulating fat metabolism means inhibiting the growth of fat cells.

Preferably, regulating fat metabolism means inhibiting accumulation of fat cells in the body.

The first panel is the change in body weight during the feeding period of each group of mice under different conditions.

The second panel is the result of oral glucose tolerance test in each group of mice.

The third graph is the area under the blood glucose curve shown in the second graph for each group of mice.

The fourth panel is the serum insulin concentration in each group of mice.

The fifth panel is the index of the insulin sensitivity in each group of mice.

The sixth panel A to the sixth panel D are the results of staining of the abdomen adipose tissue sections of the first to fourth groups of mice by hematoxylin and eosin, respectively.

In the following, in order to further illustrate the effects of the present invention, a number of examples will be described in detail, but the examples are exemplified for explanation, and any words used therein are The scope and meaning of the description of the invention and the scope of the patent application are not limited.

The composition disclosed in the present invention comprises Lactobacillus plantarum and at least one saccharide, and the Lactobacillus plantarum is often isolated from fermented foods such as kimchi, sauerkraut, fermented fruits and vegetables, and the Lactobacillus plantarum strains are numerous, for example, For example, Lactobacillus plantarum LP110 as disclosed in Japanese Patent Publication No. I453281, or Lactobacillus plantarum LP23 as disclosed in Japanese Patent Laid-Open No. I404540.

In a preferred embodiment of the invention, the composition comprises Lactobacillus plantarum LP 110, arabinogalactan and fructooligosaccharides. Further, the composition ratio of the Lactobacillus plantarum LP 110 to the arabinogalactan is 1:10 to 1:15, and the mass to volume ratio of the Lactobacillus plantarum LP 110 to the fructooligosaccharide is 50:1 to 150: 1. Specifically, the composition comprises 1 mg of Lactobacillus plantarum LP 110, 10-15 mg of arabinogalactan, and 0.0067-0.02 ml of fructooligosaccharide. Specifically, the composition ratio of the composition of the present invention is as follows: Lactobacillus plantarum LP 110 is 50 to 150 mg per kilogram per day, arabic galactan is 0.5 to 2.25 g per kilogram per day, and fructooligosaccharide is 1 ml per day. In a specific embodiment of the present invention, the dosage administered to the individual is as follows: Lactobacillus plantarum LP 110 is 200 mg per kg per day, 2.5 g per kg of arabinogalactan per day, and 2 ml of fructooligosaccharide per day. The efficacy of the compositions of the present invention can be achieved. In addition, Lactobacillus plantarum LP 110 is adapted to be administered to an individual.

By "effective amount" is meant an amount that is capable of improving or eliminating a particular symptom, symptom, disease, or disorder.

The term "prevention" refers to the ability to stop or hinder the occurrence of specific diseases and/or signs and symptoms.

The so-called "significant" means that the two sets of data are statistically analyzed. The difference is p value <0.05.

The data in the following examples are expressed as mean ± standard deviation, unless otherwise indicated, and are analyzed by Dunkindo mutation analysis after analysis by single factor variance.

Example 1: Animal test

Five-week-old mice of the male C57BL/6 (B6) strain without specific pathogens were purchased from the National Laboratory Animal Center (NLAC, Taipei, Taiwan), and the mice were adapted for 3 weeks. At the age of eight weeks, they were randomly divided into six groups, and there were 8 mice in each group. There was no significant difference in the average body weight between the groups, and each group of mice was treated under the following conditions. Week, continuous feeding until the 19th week: the first group was a blank group without any treatment; the second group was a control group, treated with 30% syrup and 60% high-fat diet, and sterilized distilled water was given at a daily dose per kilogram. 10 ml; the third group was treated with 30% syrup and 60% high-fat diet, and fed Lactobacillus plantarum powder (10 ¹² CFU/g) at a dose of 200 mg/kg per day; the fourth group was 30% syrup And 60% high-fat diet, and fed Lactobacillus plantarum powder (10 ¹² CFU / g), arabinogalactan and fructooligosaccharides, while the dosage of Lactobacillus plantarum powder is 200 mg per kilogram per day, Arabia The dose of galactan is 2.5 grams per kilogram per day, and fructooligosaccharides Daily dose of two milliliters per kilogram.

During the period from the 1st week to the 19th week of feeding, the body weight of each group of mice was recorded every week, and the results are shown in the first figure. Each group of mice was sacrificed at the 19th week of feeding, and the liver, spleen and fat of each group of mice were taken out and weighed. The results are shown in Tables 1 and 2 below.

The results of the first and Table 1 and Table 2 show that the high-sugar and high-fat diet can significantly increase the body weight of the second group of mice compared with the first group of mice, and the total weight gain of the second group of mice, liver The weight of spleen, kidney, abdominal fat, perirenal fat and sputum fat were significantly higher than those of the first group of mice. The body weight, total weight gain and visceral weight of the third group of mice were lower than those of the second group, but significantly higher than the first group of mice, and the fat weight of the organs of the third group was the same. There were no significant differences between the two groups of mice. In the fourth group of mice, the body weight, total weight gain, liver, spleen, kidney, abdominal fat, perirenal fat and weight of the adipose fat were significantly lower than those of the second group of mice.

As is well known in the art to which the present invention pertains, the liver and spleen are in an inflammatory state, and their weight is significantly increased. From the above results, it can be seen that by feeding a high-sugar and high-fat diet, the body weight, liver weight, and spleen weight of the individual are increased, and thus it is shown that high sugar is high. Fat feeds can indeed induce obesity, inflammatory responses, and hepatic metabolic syndrome in mice. Moreover, the contents of Tables 1 and 2 show that mice fed with Lactobacillus plantarum to high sugar and high fat diets can slow down their weight gain, but they cannot reduce the accumulation of fat in the internal organs, just as before. As disclosed in the art, the Lactobacillus plantarum strain cannot reduce the fat content, and thus it can be seen that the simple administration of the Lactobacillus plantarum system cannot achieve the effects of improving the inflammatory reaction and the hepatic metabolic syndrome. Only the simultaneous administration of Lactobacillus plantarum powder, arabinogalactan and fructooligosaccharide can effectively improve the obesity and inflammation response induced by high-fat and high-sugar diet, and reduce the risk of hepatic metabolic syndrome in individuals.

Therefore, the composition of the present invention has an effect of inhibiting the occurrence of obesity, an inflammatory reaction, and a liver-associated metabolic syndrome.

Example 2: Oral glucose tolerance test

Each of the mice in Example 1 was fed to the 19th week, and each of the mice was fasted for 16 hours, and each of the mice was given glucose (2.0 g/kg), before and after the glucose administration. At about 30, 60, 90, and 120 minutes, about 5 μl of each mouse tail vein blood was taken, and blood glucose levels were measured by a commercially available blood glucose meter (i-SENS, Inc, Korea), and the results are shown in the second figure, and The area under the blood glucose curve of each group is shown in the third figure.

From the results of the second figure, the blood glucose level of the second group of mice at 0 minutes after fasting for 16 hours was significantly higher than that of the first group, the third group and the fourth group of mice, and 30 after oral administration of glucose. In minutes, each group reached a peak of high blood glucose, while the blood glucose of the second group was significantly higher than that of the first group. As the monitoring time increased, the blood glucose levels of the mice in this group gradually decreased. However, at the 150th minute, the blood glucose levels of the second group of mice were significantly higher than those of the first, third and fourth groups. . From the results of the third graph, the area under the blood glucose curve of the second group is significantly higher than the first Group, third group and fourth group.

It can be seen from the above that a high-fat and high-sugar diet may cause abnormal symptoms of blood glucose metabolism in mice, and mice fed a high-fat and high-sugar diet may be administered with Lactobacillus plantarum powder alone or simultaneously. Bacterial powder, arabinogalactan and fructooligosaccharide can improve the symptoms of abnormal blood sugar metabolism. Therefore, the composition of the present invention has the effect of regulating blood sugar-related symptoms.

Example 3: Determination of insulin sensitivity

Each of the mice reared to the 19th week in Example 1 was sacrificed, blood was taken, the insulin concentration was measured using a commercially available reagent set (Mouse insulin mercodia, Uppsala, Sweden), and the insulin resistance method was evaluated according to the prior art ( matthews et al., 1985), calculates the degree of peripheral insulin sensitivity of peripheral glucose metabolism reaction indirect index (Homeostasis model assessment for insulin resistance, hereinafter referred HOMA-IR), the higher its value, the higher the representative of insulin resistance And the formula for calculating HOMA-IR is as follows: HOMA-IR = fasting insulin value (μU / ml) × fasting blood glucose value (mg / dL) ÷ 22.5 (mmol / L)

The insulin concentration and HOMA-IR values in the serum of each group of mice are shown in Fig. 2 and Fig. 3, respectively.

As shown in the results of the fourth and fifth figures, the insulin concentration and HOMA-IR values of the second group of mice were significantly higher than those of the first group of mice. Compared with the second group of mice, the insulin concentration and HOMA-IR values of the third group and the fourth group were lower, and the fourth group of mice could significantly reduce the insulin concentration and HOMA-IR value.

When the HOMA-IR value is higher than 2.5, it can be regarded as a symptom of insulin resistance. According to the results of the fifth comparison, the HOMA-IR values of the mice in the second group to the fourth group were higher than 2.5, respectively, and had symptoms of insulin resistance, respectively, in the environment of high fat and high sugar feed treatment. Only the fourth group was able to significantly reduce the HOMA-IR results.

There are many reasons for inducing insulin resistance, including abnormal glucose metabolism and abnormal lipid metabolism. Therefore, the results of the second and third examples can be reasonably inferred by simultaneously administering Lactobacillus plantarum powder, arabinogalactan and fruit In addition to regulating blood sugar, sugar can inhibit the aggregation of macrophages in fat cells and regulate lipid metabolism. Therefore, compared with the simple administration of Lactobacillus plantarum powder, the system can improve or prevent the induction of high-fat and high-sugar diet. The symptoms of insulin resistance.

Example 4: Determination of triglyceride and cholesterol in serum

The blood of each mouse after the sacrifice of Example 1 was taken, and the concentration of triglyceride and cholesterol was analyzed by a serum biochemical automatic analyzer (CoBAS MIRA PLUS, Basel, Switzerland). The results are shown in Table 3 below.

The blood biochemical reference value of the mouse from the National Experimental Animal Center showed that the concentration of serum triglyceride in normal C57BL/6JNarl mice was 123.01±35.22 mg/dl (NAR Labs web, 2008), and the results in Table 3 were compared. Compared to the pair, the first group of mice in the serum The concentration of triglyceride is higher than that of normal mice, indicating that too much triglyceride is accumulated in the body. The content of triglyceride and cholesterol in the serum of the second group of mice was significantly higher than that of the first group of mice, indicating that feeding the high-fat and high-sugar diet resulted in excessive accumulation of triglycerides and cholesterol in the mice. The content of triglyceride and cholesterol in the serum of the third group of mice was not significantly different from that of the second group of mice, indicating that mice that were directly administered to Lactobacillus plantarum to high-fat and high-glucose diet could not be reduced. The content of serum triglyceride and cholesterol. Compared with the second and third groups of mice, the serum levels of triglycerides and cholesterol in the fourth group of mice were significantly decreased, indicating that the Lactobacillus plantarum powder, arabinogalactan and fruit were simultaneously administered. The sugar system will reduce the content of triglycerides and cholesterol.

From the above results, it is understood that the composition of the present invention can effectively reduce the content of triglyceride and cholesterol in the body, and achieve the effect of preventing or treating diseases associated with abnormal lipid metabolism.

Example 5: Results of adipose tissue section staining

Take the sacrifice of the abdominal fat of each mouse after the sacrifice of Example 1 and fix it with 10% formalin. After the removal, the wax is formed, and the slice is sliced with Hematoxylin & Eosin stain (H&E stain). Dyeing. The results of staining of abdominal adipose tissue sections of each group of mice are shown in the sixth figure.

From the results of the sixth graph, the type of abdominal fat cells in the second group of mice was significantly larger than that in the first group. Compared with the second group, the size of abdominal fat cells in the third group of mice did not change significantly, while the size of abdominal fat cells in the fourth group of mice was significantly smaller.

From the above results, it can be seen that the individual administration of Lactobacillus plantarum to an individual treated with a high-fat and high-sugar diet cannot inhibit the growth of the adipocytes, and conversely, when the vegetable milk is simultaneously administered. When the bacillus powder, arabinogalactan, and fructooligosaccharide are administered to an individual treated with a high-fat, high-sugar diet, the fat cells of the individual can be significantly reduced. Accordingly, the composition of the present invention can effectively inhibit the growth of fat cells, and can achieve the symptoms of preventing or treating obesity and/or abnormal lipid metabolism caused by it.

Based on the results of the above examples, it can be confirmed that the composition of the present invention can still regulate lipid metabolism in an individual under high-fat and high-sugar diet conditions, thereby avoiding or improving fat cell growth and/or accumulation of fat cells in the body, and further It can improve or prevent diseases associated with abnormal lipid metabolism.

The present invention has been described in detail by the embodiments of the present invention. It should be understood that those skilled in the art, without departing from the spirit of the invention, The range of yokes obtained.

Claims (8)

A use of a Lactobacillus plantarum in combination with at least one saccharide for the manufacture of a composition for regulating lipid metabolism. The use according to the first aspect of the invention, wherein the Lactobacillus plantarum is Lactobacillus plantarum LP110. The use according to the first aspect of the invention, wherein the saccharide comprises arabinogalactan and fructooligosaccharide. The use according to claim 2, wherein the saccharide comprises arabinogalactan and fructooligosaccharide. The use according to the first aspect of the invention, wherein the lipid metabolism system is regulated to inhibit the growth of adipocytes. The use according to the first aspect of the invention, wherein the lipid metabolism system is regulated to inhibit accumulation of fat cells in the body. According to the application of claim 1, wherein the ratio of Lactobacillus plantarum to arabinogalactan is 1:10 to 1:15, and the ratio of the mass volume of Lactobacillus plantarum to fructooligosaccharide is 50: 1~150:1. According to the application of claim 7, wherein the composition ratio of Lactobacillus plantarum to arabinogalactan is 1:12.5, and the ratio of the mass volume of Lactobacillus plantarum to fructooligosaccharide is 100:1.