WO2018174125A1 - Composition for improving lipid metabolism - Google Patents

Abstract

The present invention pertains to a composition for improving lipid metabolism, said composition comprising a culture and/or cells of a lactic acid bacterium belonging to Streptococcus thermophilus. By taking the composition for improving lipid metabolism or a food, drug or feed for improving lipid metabolism, each comprising the aforesaid composition, lipid metabolism is improved and, as a result, body weight is reduced.

Description

Composition for improving lipid metabolism

The present invention relates to a lipid metabolism improving composition containing lactic acid bacteria belonging to Streptococcus thermophilus and foods, pharmaceuticals and feeds containing such a composition. Moreover, it is related with the composition which improves the metabolic syndrome containing the lactic acid bacteria which belong to Streptococcus thermophilus.

Fatty liver is a general term for diseases in which neutral fat is excessively deposited in the liver and causes liver damage, and is known to develop due to various factors such as excessive intake of alcohol, obesity, diabetes, and drugs. In recent years, non-alcoholic fatty liver disease (NAFLD) due to obesity, metabolic syndrome, diabetes and the like has increased rapidly, and it is said that 30% of adults are affected (Non-patent Document 1).
The cause of fat accumulation in the liver is mainly due to the inflow of fat accumulated in adipose tissue into the liver. However, in patients with NAFLD, increased fat synthesis in the liver is also a major cause, reaching 25% of the fat accumulated in the liver.
This enhancement of fat synthesis controls the expression of fatty acid synthesis-related genes such as acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), stearyl-CoA desaturase 1 (SCD1) and the expression of these fatty acid synthesis-related genes. SREBP-1c which is a transcription factor is involved. When insulin resistance is induced by obesity or metabolic syndrome, SREBP-1c is induced and the expression of fatty acid synthesis-related genes is increased, resulting in fat accumulation in the liver.

Patent Document 1 discloses a culture (a) obtained by culturing a culture medium containing at least whey protein and skim milk with Lactobacillus rhamnosus GG strain (ATCC 53103), and Lactobacillus casei TMC0409 strain (FERM P-17047). (B), a culture comprising the culture medium (c) cultured with Streptococcus thermophilus TMC1543 strain (FERM P-17046) and a calcium preparation, and containing calcium in milk solids. The functional food / beverage products which have the body fat accumulation suppression and the anti-obesity effect characterized by the said ratio being 1.5 weight% or more are disclosed.
In Patent Document 2, lactic acid bacteria are used as a prophylactic / therapeutic agent for Nonalcoholic steatohepatitis (NASH), which is a case in which hepatic tissue is accompanied by steatohepatitis associated with balloon-like swelling of hepatocytes and is at high risk of becoming cirrhosis or liver cancer. The mice were ingested with a high fat diet containing × 10 ¹⁰ / g for 12 weeks so that the daily intake was 3 g, and from the 9th week to the 12th week from the start of administration of the lactic acid bacteria-containing high fat diet When liver injury was induced by subcutaneous administration of carbon tetrachloride (first time: 0.05 ml / kg BW (body weight), second and subsequent times: 0.1 ml / kg BW) a total of 8 times a week, lactic acid bacteria were not administered. A NASH prophylactic / therapeutic agent comprising a lactic acid bacterium whose serum ALT value is reduced by 65% or more as compared with a mouse is disclosed.

By the way, with recent changes in eating habits and lifestyle habits, mainly in developed countries, obesity, especially visceral fat type obesity, two or more symptoms of hyperglycemia, hypertension and dyslipidemia have accumulated in one individual. The number of patients with metabolic syndrome, which is a condition, is increasing, which is a major social problem.
Obesity is mainly caused by the enlargement of fat cells, but it is known that fat cells have two types of cells, white fat cells and brown fat cells, which have different roles (non-patented). Reference 2).
White fat cells accumulate fat in the form of triglycerides and store energy. Therefore, when fat accumulates excessively in white fat cells and becomes enlarged, it becomes obese. When the enlarged white adipocytes secrete inflammatory cytokines such as MCP1 (Monocyte chemical protein 1), insulin resistance is induced from a chronic inflammatory state, causing lifestyle-related diseases including diabetes. It is considered.
Brown fat cells, on the other hand, accumulate fat in the cells like white fat cells, but by burning fat and producing heat by the action of UCP1 (uncoupling protein 1) present on its mitochondrial membrane. Consume energy.
That is, in the living body, the balance of energy and body fat of the whole body is adjusted by storing energy by white fat cells and consuming energy by heat production of brown fat cells.
In addition, recent studies have revealed that there are “inducible” brown adipocytes that are induced to differentiate from white adipose precursor cells in white adipose tissue due to various environmental factors (Non-patent Document 2).

Patent Document 3 aims to provide an agent for promoting differentiation from stem cells to brown adipocytes, which can improve and prevent obesity and metabolic syndrome, from stem cells containing catechins as active ingredients to brown adipocytes. Differentiation promoters, pharmaceuticals containing the differentiation promoters, quasi drugs, cosmetics and foods and drinks are disclosed as solution means.
Patent document 4 aims to provide a composition for enhancing or increasing muscles or improving metabolic syndrome and improving QOL, and a composition comprising triterpenes and polyphenols, preferably oleanolic acid and oleuropein In addition, pharmaceutical compositions and foods containing the composition are disclosed as solving means.

JP 2010-57465 A JP 2014-24776 A JP 2014-65672 A Japanese Unexamined Patent Publication No. 2016-199536

Eguchi Y. et. al. , J .; Gastroenterrol, 2012, 47: 586-595 Kajimura S. Et. Al. Cell Metab. , 2010, 11: 257-262

However, the lactic acid bacteria culture of Patent Document 1 is a mixture of the above three types of lactic acid bacteria cultures (a) to (c), and it is unclear which lactic acid bacteria have body fat accumulation suppression and anti-obesity effects. there were. Patent Document 2 mentions Streptococcus thermophilus as the lactic acid bacterium to be tested, but has verified the effect on liver damage induced by carbon tetrachloride, and does not describe any effect of improving lipid metabolism. It was. That is, no means for improving lipid metabolism using lactic acid bacteria has been reported in Patent Document 1 or Patent Document 2.
Therefore, there has been a demand for means for improving lipid metabolism using lactic acid bacteria.
The first problem of the present invention is as a new solution for improving lipid metabolism, a composition for improving lipid metabolism, comprising a lactic acid bacterium belonging to Streptococcus thermophilus as an active ingredient, and a food for improving lipid metabolism comprising the composition Providing pharmaceuticals and feed.

On the other hand, Non-Patent Document 2 discloses white adipocytes and brown adipocytes, but no method for improving adipocyte metabolism using lactic acid bacteria has been reported. Patent Documents 3 and 4 disclose methods for improving and preventing metabolic syndrome, but no method using lactic acid bacteria has been reported.
For this reason, there has been a demand for improvement and prevention of a method for improving metabolism of adipocytes and metabolic syndrome using lactic acid bacteria.
The second object of the present invention is to provide a composition for improving the metabolism of a new adipocyte and a food, a pharmaceutical and a feed for improving the metabolism of an adipocyte comprising such a composition. A second object of the present invention is to provide a composition for improving a new metabolic syndrome, and a food, a medicine and a feed for improving the metabolic syndrome including the composition.

In order to solve the first problem, the present inventors have conducted extensive studies on a composition for improving lipid metabolism in a living body, and as a result, found that lactic acid bacteria belonging to Streptococcus thermophilus have these improving actions. The present invention has been completed. That is, the first invention relates to the following contents.
(A1) A composition for improving lipid metabolism comprising, as an active ingredient, a culture of lactic acid bacteria and / or bacterial cells belonging to Streptococcus thermophilus (Streptococcus thermophilus).
(A2) The lactic acid bacterium belonging to Streptococcus thermophilus is Streptococcus thermophilus SBT1
The composition for improving lipid metabolism according to (A1), which is any one of 277 (FERM BP-03234) and SBT1063 (NITE P-02398).
(A3) The composition for improving lipid metabolism according to (A1) or (A2), wherein the lipid metabolism is lipid metabolism in the liver.
(A4) A food for improving lipid metabolism comprising the composition for improving lipid metabolism according to any one of (A1) to (A3).
(A5) A drug for improving lipid metabolism comprising the composition for improving lipid metabolism according to any one of (A1) to (A3).
(A6) A lipid metabolism improving feed comprising the lipid metabolism improving composition according to any one of (A1) to (A3).
(A7) Streptococcus thermophilus SBT-1063 (NITE P-02398), which is a novel lactic acid bacterium belonging to Streptococcus thermophilus.

In order to solve the second problem, the present inventors have conducted extensive studies on a composition that suppresses accumulation of excess fat and obesity in a living body and a composition that improves metabolic syndrome, and as a result, Streptococcus thermophilus The present invention was completed by finding that these have an improving action. That is, the second invention relates to the following contents.
(B1) A composition for promoting differentiation from white adipose precursor cells to brown adipocytes, comprising a lactic acid bacteria culture and / or cells belonging to Streptococcus thermophilus as an active ingredient.
(B2) The composition according to (B1), wherein the lactic acid bacterium belonging to Streptococcus thermophilus is Streptococcus thermophilus SBT1277 (FERM BP-03234).
(B3) A composition for activating brown adipocytes comprising a culture of lactic acid bacteria belonging to Streptococcus thermophilus and / or bacterial cells as an active ingredient.
(B4) The composition according to (B3), wherein the lactic acid bacterium belonging to Streptococcus thermophilus is Streptococcus thermophilus SBT1277 (FERM BP-03234).
(B5) A composition for improving metabolic syndrome, comprising a culture of lactic acid bacteria and / or cells belonging to Streptococcus thermophilus as an active ingredient.
(B6) The lactic acid bacterium belonging to Streptococcus thermophilus is Streptococcus thermophilus SBT1277 (FERM BP-03234).
(B7) A food for promoting differentiation from white adipose precursor cells to brown adipocytes, comprising the composition according to (B1) or (B2).
(B8) A pharmaceutical product for promoting differentiation from white adipose precursor cells to brown adipocytes, comprising the composition according to (B1) or (B2).
(B9) A feed for promoting differentiation from white adipose precursor cells to brown adipocytes, comprising the composition according to (B1) or (B2).
(B10) A food product for activating brown adipocytes, comprising the composition according to (B3) or (B4).
(B11) A pharmaceutical product for activating brown adipocytes, comprising the composition according to (B3) or (B4).
(B12) A feed for activating brown adipocytes, comprising the composition according to (B3) or (B4).
(B13) A food for improving metabolic syndrome, comprising the composition according to (B5) or (B6).
(B14) A drug for improving metabolic syndrome, comprising the composition according to (B5) or (B6).
(B15) A feed for improving metabolic syndrome, comprising the composition according to (B5) or (B6).
Further, the second problem includes the configuration of a fatty acid synthesis inhibitor, a cholesterol synthesis inhibitor, a gluconeogenesis inhibitor, or an adipose tissue inflammation inhibitor containing lactic acid bacteria belonging to Streptococcus thermophilus as an active ingredient. .

The first invention provides a lipid metabolism improving composition containing lactic acid bacteria belonging to Streptococcus thermophilus and a lipid metabolism improving food, pharmaceutical and feed containing the composition as a new solution for improving lipid metabolism To do.
Therefore, improvement of lipid metabolism can be expected in a simple and safe manner by ingesting the above composition, food, medicine and feed of the present invention.

The second invention is a lipid metabolism improving composition containing lactic acid bacteria belonging to Streptococcus thermophilus as a new solution for suppressing the accumulation of excess fat and obesity in a living body. The present invention provides a composition for improving lipid metabolism that improves the metabolism of adipocytes, such as promoting differentiation into cells and activating brown adipocytes, and foods, pharmaceuticals, and feeds containing such compositions.
In addition, the second invention is a new solution for improving metabolic syndrome, a composition for improving metabolic syndrome including lactic acid bacteria belonging to Streptococcus thermophilus, and a food, a medicine for improving metabolic syndrome containing such a composition, And providing feed.
Therefore, improvement of adipocyte metabolism and metabolic syndrome can be expected in a simple and safe manner by ingesting the above composition, food, medicine and feed of the second invention.

[A: First invention]
The present inventors have conceived that it is possible to prevent the accumulation of fat in the liver by suppressing the synthesis of fat in the liver in addition to suppressing the accumulation of fat in the adipose tissue. As a result of intensive research, it was found that lactic acid bacteria belonging to Streptococcus thermophilus prevent the accumulation of fat in the liver. The first invention is based on the above findings.
(Active ingredient)
The present invention relates to a lipid metabolism improving composition containing lactic acid bacteria belonging to Streptococcus thermophilus and foods, pharmaceuticals, and feeds containing the same, and Streptococcus thermophilus used in the present invention is a 16S ribosomal RNA gene sequence analysis. Any lactic acid bacteria can be used as long as they are classified into Streptococcus thermophilus species by a general classification method such as the above.
In the present invention, in particular, Streptococcus thermophilus SBT1277 (FERM BP-3234), SBT1063 (NITE P-02398), SBT1021A (FERM P-10358), SBT10137 (FERM P19530, FERM P-19531) -9442), SBT0113 (FERM P-9443), SBT0144 (FERM P-16638), SBT1035 (FERM P-16945) and ATCC 19258, among which SBT1063 (NITE P-02398), SBT1277 (FERM BP- 03234) is particularly preferred.
Strains having numbers starting with FERM or NITE in parentheses can be obtained from the depository organizations described later, and ATCC 19258 can be purchased from the American Type Culture Collection, an American microorganism distribution organization.
Streptococcus thermophilus used in the present invention may be live cells, dead cells, cell cultures, cytoplasm or cell wall fractions obtained by treating these cells with enzymes or physical means, One or more of these can be used.

(Preparation of a composition containing Streptococcus thermophilus)
A composition containing lactic acid bacteria belonging to Streptococcus thermophilus, which is an active ingredient of the present invention, can be obtained according to a conventional method for preparing a culture of lactic acid bacteria. For the culture, various media such as a milk medium or a medium containing milk components and a semi-synthetic medium not containing the milk medium can be used.
The culture of lactic acid bacteria can be obtained by inoculating the sterilized medium with lactic acid bacteria belonging to Streptococcus thermophilus and culturing at about 20 ° C. to 45 ° C. for 5 hours to several days. The culture temperature and period may be appropriately adjusted according to the Streptococcus thermophilus strain used and the desired number of bacteria.
The culture containing lactic acid bacteria belonging to Streptococcus thermophilus obtained by culturing can be used as a composition containing lactic acid bacteria belonging to Streptococcus thermophilus as an active ingredient of the present invention as it is. A composition obtained by subjecting the culture to a treatment such as centrifugation, membrane concentration, drying, or freeze-drying can also be used.
As an embodiment of a method for preparing a composition containing Streptococcus thermophilus, a 11.55% skim milk medium supplemented with 0.5% yeast extract (manufactured by Asahi Breweries) is sterilized at 115 ° C. for 20 minutes. An example of the preparation method includes a step of inoculating Streptococcus thermophilus SBT1277 (FERM BP-03234) after cooling to room temperature, culturing at 37 ° C. for 16 hours, and freeze-drying and pulverizing the obtained culture in a mortar.

(Intake of active ingredients)
The intake amount of lactic acid bacteria belonging to Streptococcus thermophilus which is an active ingredient of the present invention (the number of bacteria per day) may be 5 × 10 ⁸ or more in the case where Streptococcus thermophilus is viable, 1 × 10 ¹⁰ or more is more preferable, and 1 × 10 ¹¹ or more is most preferable.
When Streptococcus thermophilus is dead, it may be an amount corresponding to the number of bacteria equivalent to the above live bacteria. When both live and dead bacteria are included, the total of the live and dead bacteria may be an amount corresponding to the number of bacteria equivalent to the above live bacteria.
In the case of cytoplasm or cell wall fraction obtained by treating bacterial cells with enzymes or physical means, the daily intake per adult may be 0.1 mg to 5000 mg, preferably 100 mg to 2500 mg, preferably 500 mg More preferably, it is 1000 mg or less.

(Effectiveness)
The composition for improving lipid metabolism containing lactic acid bacteria belonging to Streptococcus thermophilus of the present invention and the food, medicine and feed containing the composition, the expression of fatty acid synthesis related genes in the liver by ingesting the above intake , Reducing the accumulation of triglycerides and total lipids in the liver, reducing plasma triglyceride levels, and further reducing body weight.
Lipid abnormalities that occur when the balance of cholesterol and triglycerides (neutral fat) in the blood is lost by ingesting the above-described composition for improving lipid metabolism and foods, pharmaceuticals, and feeds containing such compositions. Prevention and improvement of this are expected. Furthermore, diseases caused by dyslipidemia (eg, insulin resistance, diabetes, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, cirrhosis, liver cancer) and arteriosclerotic diseases (eg, hypertension, narrowing) Prevention and improvement of cardiomyopathy, myocardial infarction, cerebral infarction, cerebral hemorrhage, aortic aneurysm, renal infarction, obstructive arteriosclerosis are expected.

(Evaluation of effectiveness)
The composition for improving lipid metabolism containing lactic acid bacteria belonging to Streptococcus thermophilus and the effect on lipid metabolism of foods, pharmaceuticals, and feeds containing such a composition according to the present invention are described in Example A in vitro or in vivo. It can be evaluated by the following test.

(Foods, pharmaceuticals, and feeds containing a composition containing Streptococcus thermophilus)
The composition containing Streptococcus thermophilus of the present invention can be blended in any food, and the amount of the composition is adjusted in consideration of the intake of the above-mentioned active ingredients. It only has to be manufactured.
Examples of foods include cheese, fermented milk, dairy lactic acid bacteria beverages, lactic acid bacteria beverages, butter, margarine and other dairy products, milk beverages, fruit juice beverages, soft drinks and other beverages, jelly, candy, pudding, mayonnaise and other egg processing Goods, confectionery such as butter cake, bread, and various types of powdered milk, infant foods, nutritional compositions, and the like can be exemplified.

The composition containing Streptococcus thermophilus of the present invention can be blended in any medicine, and the amount of the composition is adjusted in consideration of the intake of the above-mentioned active ingredients. It may be manufactured by.

The composition containing Streptococcus thermophilus of the present invention can be blended in any feed, and the blending amount of the composition is adjusted in consideration of the intake amount of the above-mentioned active ingredients. It may be manufactured by.

[Example A]
Example A and Test Example A are shown below and the present invention will be described in detail, but the present invention is not limited by these.
[Example A1] Preparation of a composition containing Streptococcus thermophilus 0.5% yeast extract (manufactured by Asahi Breweries) sterilized by Streptococcus thermophilus SBT1277 (FERM BP-03234) at 115 ° C for 20 minutes The culture was carried out at 37 ° C. for 16 hours in the added 11.55% skim milk medium for 3 or more generations and activated. This was inoculated with 3% of the same medium and cultured at 37 ° C. for 16 hours. The obtained culture was freeze-dried and then pulverized in a mortar to obtain a composition containing powdered Streptococcus thermophilus.
The number of viable bacteria of Streptococcus thermophilus SBT1277 in the above composition was 3.6 × 10 ⁹ cfu / g.

[Test Example A1] Effect of various lactic acid bacteria on fatty acid synthesis-related gene expression in hepatocytes The effect of various lactic acid bacteria on fatty acid synthesis-related gene expression in hepatocytes was examined.
1. Test method 1-1. Cell Culture Method HepG2 cells, which are established hepatoma cells, were seeded in 12-well plates and cultured in 10% FBS-containing DMEM medium until confluent. After further overnight culture in FBS-free DMEM medium, skim milk medium (final concentration 5 mg / mL), or skim milk culture of lactic acid bacteria of (1) to (5) below (final concentration 5 mg / mL) are added. Then, the medium was replaced with each added FBS-free DMEM medium and cultured for 2 days. Here, strains with numbers starting with JCM can be purchased from the Microbial Materials Development Department, RIKEN BioResource Center. In addition, strains with numbers beginning with ATCC can be purchased from the American Type Culture Collection, an American microorganism distribution agency.
<Lactic acid bacteria>
(1) Lactobacillus gasseri (JCM1131)
(2) Bifidobacterium longum (JCM1217)
(3) Lactobacillus helveticus (JCM1120)
(4) Lactobacillus delbrueckii subsp. Bulgaricus (ATCC 11842)
(5) Streptococcus thermophilus (ATCC 19258)

1-2. Analysis of gene expression Thereafter, total RNA was extracted from the cultured cells using Sepazol RNA I SuperG reagent (manufactured by Nacalai Tesque). Reverse transcription reaction is ReverseTra Ace qPCR
RT Master Mix (Toyobo Co., Ltd.) was used. Using the obtained cDNA, real-time PCR was performed with THUNDERBIRD qPCR Mix (manufactured by Toyobo Co., Ltd.), and the expression level of fatty acid synthesis-related genes (SREBP-1c, FAS, SCD1) was quantified.
As an internal standard for evaluating the gene expression level, the expression level of Cyclophilin gene was used, and the following primers were used for the analysis.
SREBP1c-F; TCGCGGAGCCATGGATT (SEQ ID NO: 1)
SREBP1c-R; GCCAGGGAAGTCACTGTCTTG (SEQ ID NO: 2 in the sequence listing)
FAS-F; GCAAATTCGACCTTTCTCAGAAC (SEQ ID NO: 3)
FAS-R; GGACCCCGTGGAAATTCA (SEQ ID NO: 4)
SCD1-F; TGTGGAGCCCACCCTCTTAC (SEQ ID NO: 5)
SCD1-R; ACGAGCCCATTCATAGACATCA (SEQ ID NO: 6 in the sequence listing)
Cyclophilin-F; GCGTCTCCTTTGAGCTGTTTG (SEQ ID NO: 7)
Cyclophilin-R; ATCCTTTCTCTCCAGTGCTCAGA (SEQ ID NO: 8)

2. Test results The results are shown in Table A1. Streptococcus thermophilus skim milk cultures significantly reduced the expression of fatty acid synthesis-related genes in hepatocytes. On the other hand, skim milk cultures of Lactobacillus gasseri, Bifidobacterium longum, Lactobacillus helveticus and Lactobacillus bulgaricus hardly changed the expression of fatty acid synthesis-related genes.

[Test Example A2] Effect of Streptococcus thermophilus on expression of fatty acid synthesis-related genes in hepatocytes The effect of Streptococcus thermophilus on expression of fatty acid synthesis-related genes in hepatocytes was examined.
1. Test Method As in Test Example A1, after seeding HepG2 cells in a 12-well plate and culturing, skim milk medium (final concentration 1 mg / mL), Streptococcus thermophilus ATCC 19258, or SBT1277 (FERM BP-3234), or SBT1063 (NITE P-02398) nonfat milk culture (the final concentration was 0.1, 0.5, 1 mg / mL) was replaced with FBS-free DMEM medium and cultured for 2 days. Thereafter, RNA was purified in the same manner as in Test Example A1, and the expression level of fatty acid synthesis-related genes (SREBP-1c, FAS) was quantified.

2. Test results The results are shown in Table A2. Streptococcus thermophilus SBT1277 and SBT1063 reduced the expression of fatty acid synthesis-related genes in hepatocytes even at concentrations of 1 mg / mL or less, which is not different in Streptococcus thermophilus ATCC 19258.

[Test Example A3] Effect of Streptococcus thermophilus on accumulation of triglyceride in hepatocytes The effect of Streptococcus thermophilus on accumulation of triglyceride in hepatocytes was examined.
1. Test Method As in Test Example A1, HepG2 cells are seeded in a 12-well plate and cultured, and then skim milk medium (final concentration 0.2 mg / mL), Streptococcus thermophilus ATCC 19258, SBT1277, or SBT1063 skim milk culture The culture medium was replaced with an FBS-free DMEM medium supplemented with a product (both at a final concentration of 0.5 mg / mL) and cultured for 2 days. The cells were disrupted in extraction buffer (50 mM Tris-HCl, pH 7.5, 0.1% Triton X-100) and centrifuged, and the triglyceride concentration in the supernatant was determined as triglyceride E test Wako (manufactured by Wako Pure Chemical Industries, Ltd.). It measured using. The protein concentration was measured using a BCA protein assay (manufactured by Thermo Fisher Scientific).

2. Test results The results are shown in Table A3. All Streptococcus thermophilus significantly reduced triglyceride accumulation in the cells compared to the control, but the effect was higher in Streptococcus thermophilus SBT1277 and SBT1063 compared to Streptococcus thermophilus ATCC 19258. Streptococcus thermophilus SBT1277 was the most effective.

[Test Example A4] Lipid metabolism improving effect of Streptococcus thermophilus SBT1277 (FERM BP-03234) The lipid metabolic improving effect of Streptococcus thermophilus SBT1277 (FERM BP-3234) was examined using mice.
1. Test method 1-1. Breeding method After 5 weeks old male C57BL6 / JJcl mice were acclimated for 1 week, 20 mice were bred in 2 groups and kept for 8 weeks under the following conditions so that there was no difference in average body weight.
(1) Control group Based on the AIN76 feed, a high fat diet prepared to contain 20% skim milk medium and 20% fat was fed.
(2) Thermofils group Instead of the skim milk medium of the control group feed, a high fat diet prepared to contain 20% of the Streptococcus thermophilus SBT1277 skim milk culture prepared in Example A1 was fed.

1-2. Measurement method (1) Body weight and plasma triglyceride concentration After measuring the body weight, blood was collected and the liver was removed. Triglyceride concentration was measured using plasma prepared from blood. For the measurement, Triglyceride E-Test Wako was used.
(2) Analysis of gene expression RNA was extracted from the liver, and the expression level of fatty acid synthesis-related genes was analyzed by the same method as in Test Example A2.
(3) Liver lipid concentration Lipids were extracted from the liver with chloroform / methanol, and the total lipid concentration and triglyceride concentration were measured. The total lipid concentration was measured by weighing the lipid weight after extraction, and the triglyceride concentration was measured using Triglyceride E-Test Wako after dissolving the extracted lipid in isopropanol. Moreover, the density | concentration per 1g liver was computed by remove | dividing each measured value by the weight of the liver used for extraction.

2. Test results (1) Body weight, liver weight, plasma triglyceride concentration The results are shown in Table A4. The thermophilus group had a significant weight loss compared to the control group. Plasma triglyceride levels were also significantly reduced.

(2) Expression of fatty acid synthesis-related genes The results are shown in Table A5. The expression level of fatty acid synthesis-related genes in the liver was significantly reduced in the Thermophilus group compared to the control group.

(3) Liver lipid concentration The results are shown in Table A6. In the Thermophilus group, the total lipid and triglyceride concentrations in the liver tended to decrease compared to the control group.

From these results, it was found that Streptococcus thermophilus improves the metabolism and lowers the body weight by reducing the neutral fat in the blood and suppressing the accumulation of fat in the liver.

[Example A2] Production of composition for improving lipid metabolism Centrifugation of Streptococcus thermophilus SBT1277 M17 medium (manufactured by OXOID) at 4 ° C. and 7000 rpm for 15 minutes, followed by washing with sterile water and centrifugation Repeated 3 times to obtain washed cells. The washed cells were freeze-dried to obtain cell powder. This can be used as it is as a composition for improving lipid metabolism.
The viable cell count of Streptococcus thermophilus SBT1277 in the above composition was 1.6 × 10 ¹¹ cfu / g.

[Example A3] Manufacture of a drug for improving lipid metabolism 4 parts of skimmed milk powder were mixed with 1 part of the bacterial powder prepared in Example A2, and this mixed powder was tableted 1 g at a time by a conventional method, A tablet containing 200 mg of cells of Streptococcus thermophilus SBT1277 was prepared.

[Example A4] Production of fermented milk for improving lipid metabolism 10% reduced skim milk medium was sterilized at 115 ° C for 15 minutes, then inoculated with Streptococcus thermophilus SBT1277, cultured at 37 ° C for 16 hours, and skim milk culture Was prepared. Fermented milk (16% nonfat dry milk + 3% glucose) sterilized at 100 ° C. for 10 minutes was inoculated and fermented at 39 ° C. for 10 hours to obtain fermented milk for lipid metabolism improvement.
The viable cell count of Streptococcus thermophilus SBT1277 in the above fermented milk was 1.8 × 10 ⁹ cfu / g.

[Example A5] Production of lactic acid bacteria beverage for improving lipid metabolism Streptococcus thermophilus SBT1277 cultured in 10% reduced skim milk medium was sterilized at 95 ° C. for 90 minutes in 10 g of fermented mix (16% nonfat dry milk + 3% glucose) 3% Then, the mixture was cultured at 35 ° C. for 20 hours. 10 g of this culture was mixed with 40 g of isomerized sugar (BRIX 15%) to obtain a lactic acid bacteria beverage for improving lipid metabolism.
The number of viable bacteria of Streptococcus thermophilus SBT1277 in the above lactic acid bacteria beverage was 4 × 10 ⁸ cfu / g.

[Example A6] Production of composition for improving lipid metabolism After sterilization of reduced skim milk medium (13% by weight skim milk powder, 0.5% yeast extract) at 95 ° C for 30 minutes, Streptococcus thermophilus SBT1277 was inoculated. After culturing at 37 ° C. for 16 hours, the obtained culture was centrifuged at 5000 rpm for 20 minutes to obtain a culture supernatant from which the precipitate was removed. This can be used as it is as a composition for improving lipid metabolism.

[Example A7] Production of health food for improving lipid metabolism 50 g of the culture powder of Streptococcus thermophilus SBT1277 obtained in Example A1, 40 g of an equal mixture of vitamin C and citric acid, 100 g of granulated sugar, corn starch and lactose 60 g of an equal amount of the mixture was added and mixed. The mixture was packed in a stick-shaped bag to obtain a health food for improving lipid metabolism.

[Example A8] Manufacture of feed for improving lipid metabolism Soybean meal 12 kg, skim milk powder 14 kg, soybean oil 4 kg, corn oil 2 kg, palm oil 23.2 kg, corn starch 14 kg, wheat flour 9 kg, bran 2 kg, vitamin mixture 5 kg, cellulose 2 8 kg and 2 kg of the mineral mixture were sterilized at 120 ° C. for 4 minutes, and 10 kg of the culture powder of Streptococcus thermophilus SBT1277 obtained in Example A1 was blended to produce a feed for improving lipid metabolism.

[Example A9] Production of cheese for improving lipid metabolism The raw material milk was sterilized by heating (75 ° C, 15 seconds), cooled to 30 ° C, and 0.01% calcium chloride was added. Furthermore, 0.7% of commercially available lactic acid bacteria starter (LD starter, Christian Hansen) and 1% of Streptococcus thermophilus SBT1277 culture were added, and 0.003% of rennet was further added to coagulate the milk. The curd thus obtained was cut and stirred until the pH was 6.2 to 6.1, and the whey was discharged to obtain curd grains. Then, the curd grains were packed, pressed, further salted, and aged at 10 ° C. to produce Gouda cheese type hard natural cheese for improving lipid metabolism containing Streptococcus thermophilus SBT1277.
[B: Second invention]
The present inventors improve metabolism in adipocytes, promote differentiation from white adipose precursor cells to brown adipocytes, or activate brown adipocytes to enhance energy consumption by heat production. The idea was to suppress the accumulation of excess fat and obesity in the living body, and to prevent or improve metabolic syndrome and the like. As a result of intensive research, it was found that lactic acid bacteria belonging to Streptococcus thermophilus promote differentiation of white adipose precursor cells to brown adipocytes or activate brown adipocytes. The second invention is based on the above findings.
(Active ingredient)
The present invention relates to a composition for improving lipid metabolism that promotes differentiation of white adipose precursor cells containing lactic acid bacteria belonging to Streptococcus thermophilus into brown adipocytes, a composition for activating brown adipocytes, and a composition for improving metabolic syndrome metabolism. And foods, medicines and feeds containing them.
As the Streptococcus thermophilus used in the present invention, any lactic acid bacteria classified into Streptococcus thermophilus species by a general classification method such as 16S ribosomal RNA gene sequence analysis can be used.
In the present invention, in particular, Streptococcus thermophilus SBT1277 (FERM BP-3234), SBT1063 (NITE P-02398), SBT1021A (FERM P-10358), SBT10137 (FERM P19530, FERM P-19531) −9442), SBT0113 (FERM P-9443), SBT0144 (FERM P-16638), SBT1035 (FERM P-16945), and ATCC 19258, among which SBT1277 (FERM BP-3234) is particularly preferable.
Strains having numbers starting with FERM or NITE in parentheses can be obtained from the depository organizations described later, and ATCC 19258 can be purchased from the American Type Culture Collection, an American microorganism distribution organization.
Streptococcus thermophilus used in the present invention may be live cells, dead cells, cell cultures, cytoplasm or cell wall fractions obtained by treating these cells with enzymes or physical means, One or more of these can be used.

(Preparation of a composition containing Streptococcus thermophilus)
A composition containing lactic acid bacteria belonging to Streptococcus thermophilus, which is an active ingredient of the present invention, can be obtained according to a conventional method for preparing a culture of lactic acid bacteria.
For the culture, various media such as a milk medium or a medium containing milk components and a semi-synthetic medium not containing the milk medium can be used.
The culture of lactic acid bacteria can be obtained by inoculating the sterilized medium with lactic acid bacteria belonging to Streptococcus thermophilus and culturing at about 20 ° C. to 45 ° C. for 5 hours to several days. The culture temperature and period may be appropriately adjusted according to the Streptococcus thermophilus strain used and the desired number of bacteria.
The culture containing lactic acid bacteria belonging to Streptococcus thermophilus obtained by culturing can be used as a composition containing lactic acid bacteria belonging to Streptococcus thermophilus as an active ingredient of the present invention as it is. A composition obtained by subjecting the culture to a treatment such as centrifugation, membrane concentration, drying, or freeze-drying can also be used.
As an embodiment of a method for preparing a composition containing Streptococcus thermophilus, a 11.55% skim milk medium supplemented with 0.5% yeast extract (manufactured by Asahi Breweries) is sterilized at 115 ° C. for 20 minutes. Examples of the preparation method include a step of inoculating Streptococcus thermophilus after cooling to room temperature, culturing at 37 ° C. for 16 hours, freeze-drying the obtained culture, and grinding in a mortar.

(Intake of active ingredients)
The intake amount of lactic acid bacteria belonging to Streptococcus thermophilus which is an active ingredient of the present invention (the number of bacteria per day) may be 5 × 10 ⁸ or more in the case where Streptococcus thermophilus is viable, 1 × 10 ¹⁰ or more is more preferable, and 1 × 10 ¹¹ or more is most preferable.
When Streptococcus thermophilus is dead, it may be an amount corresponding to the number of bacteria equivalent to the above live bacteria. When both live and dead bacteria are included, the total of the live and dead bacteria may be an amount corresponding to the number of bacteria equivalent to the above live bacteria.
In the case of cytoplasm or cell wall fraction obtained by treating bacterial cells with enzymes or physical means, the daily intake per adult may be 0.1 mg to 5000 mg, preferably 100 mg to 2500 mg, preferably 500 mg More preferably, it is 1000 mg or less.

(Effectiveness)
The composition containing lactic acid bacteria belonging to the Streptococcus thermophilus of the present invention, and the food, medicine and feed containing such a composition differentiate white fat precursor cells into brown fat cells when ingested at the above intake. Brown fat cells are activated, and subcutaneous fat and visceral fat are reduced and body weight is reduced.
Furthermore, the composition containing the lactic acid bacteria belonging to Streptococcus thermophilus of the present invention as an active ingredient, and the food, medicine, and feed containing the composition are expressed in the amount of fatty acid synthesis-related gene by ingesting at the above intake. Is suppressed, the expression of cholesterol synthesis-related genes is suppressed, and the expression of gluconeogenesis-related genes is suppressed, thereby improving the metabolic syndrome.

Lipid abnormalities that occur when the balance of cholesterol and triglycerides (neutral fat) in the blood is lost by ingesting the above-described composition for improving lipid metabolism and foods, pharmaceuticals, and feeds containing such compositions. Prevention and improvement of this are expected. Furthermore, diseases caused by dyslipidemia (eg, insulin resistance, diabetes, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, cirrhosis, liver cancer) and arteriosclerotic diseases (eg, angina pectoris) Prevention or improvement of myocardial infarction, cerebral infarction, cerebral hemorrhage, aortic aneurysm, renal infarction, obstructive arteriosclerosis).

(Evaluation of effectiveness)
The composition of the present invention comprising a lactic acid bacterium belonging to Streptococcus thermophilus as an active ingredient, and the effect of improving the metabolism of adipocytes in foods, pharmaceuticals, and feeds containing the composition are the in vivo described in Example B. It can be evaluated by testing.

(Foods, pharmaceuticals, and feeds containing a composition containing Streptococcus thermophilus)
The composition containing Streptococcus thermophilus of the present invention can be blended in any food, and the blending amount of the composition is adjusted in consideration of the intake amount of the above active ingredients. It only has to be manufactured.
Examples of foods include dairy products such as cheese, fermented milk, dairy lactic acid bacteria beverages, lactic acid bacteria beverages, butter and margarine, beverages such as dairy beverages, fruit juice beverages and soft drinks, and egg processed products such as jelly, candy, pudding and mayonnaise In addition, confectionery and breads such as butter cake, and various types of powdered milk, infant foods, nutritional compositions and the like can be exemplified.

The composition containing Streptococcus thermophilus of the present invention can be blended in any pharmaceutical, and the blending amount of the composition is adjusted in consideration of the intake amount of the above-mentioned active ingredients, otherwise the standard method of the desired pharmaceutical It may be manufactured according to

The composition containing Streptococcus thermophilus of the present invention can be blended in any feed, and the blending amount of the composition is adjusted in consideration of the intake amount of the above-mentioned active ingredients. It may be manufactured according to

[Example B]
Example B and Test Example B are shown below, and the present invention will be described in detail, but the present invention is not limited thereto.

Example B1: Preparation of a composition containing Streptococcus thermophilus
Streptococcus thermophilus SBT1277 (FERM BP-03234) was sterilized at 115 ° C. for 20 minutes and added with 0.5% yeast extract (Asahi Breweries) at 11.55% skim milk medium at 37 ° C., 16 It was activated by culturing for 3 or more times. This was inoculated with 3% of the same medium and cultured at 37 ° C. for 16 hours. The obtained culture was freeze-dried and then pulverized in a mortar to obtain a composition containing powdered Streptococcus thermophilus.
The number of viable bacteria of Streptococcus thermophilus SBT1277 in the above composition was 3.6 × 10 ⁹ cfu / g.

[Test Example B1]
Using mice, the metabolic improvement effect of Streptococcus thermophilus was examined.
1. Test method 1-1. Breeding method After 5 weeks old male C57BL6 / JJcl mice were acclimated for 1 week, 20 mice were bred in 2 groups and kept for 8 weeks under the following conditions so that there was no difference in average body weight.
(1) Control group AIN76 feed was fed with a high fat diet prepared to contain 20% skim milk medium and 20% fat.
(2) Thermofils group Instead of the skim milk medium of the control group feed, a high fat diet prepared to contain 20% of a composition (fat milk culture) containing Streptococcus thermophilus SBT1277 prepared in Example B1 Ingested

1-2. Measurement method (1) Body weight, weight of each tissue, plasma parameter After measuring body weight, blood, liver, groin adipose tissue, peritesticular adipose tissue, mesenteric adipose tissue, interscapular brown adipose tissue were collected.
Triglyceride and insulin concentrations were measured using plasma prepared from blood. Triglyceride E-Test Wako was used for measurement of triglyceride concentration, and an ultrasensitive mouse insulin measurement kit (manufactured by Morinaga Bioscience Laboratories) was used for insulin measurement.
(2) Liver total lipid and liver triglyceride concentration Lipids were extracted from the liver with chloroform / methanol, and the total lipid concentration and triglyceride concentration were measured. The total lipid concentration was measured by weighing the lipid weight after extraction, and the triglyceride concentration was measured using Triglyceride E-Test Wako after dissolving the extracted lipid in isopropanol. Moreover, the density | concentration per 1g liver was computed by remove | dividing each measured value by the weight of the liver used for extraction.

(3) Analysis of gene expression Total RNA was extracted from each tissue using Sepazol RNA I SuperG reagent (manufactured by Nacalai Tesque). For reverse transcription reaction, ReverseTra Ace qPCR RT Master Mix (manufactured by Toyobo Co., Ltd.) was used. Using the obtained cDNA, real-time PCR was performed with THUNDERBIRD qPCR Mix (manufactured by Toyobo Co., Ltd.), and the expression level of the gene was analyzed.
In the liver, the expression of fatty acid synthesis-related genes (SREBP-1c, FAS, SCD1), cholesterol synthesis-related gene (SREBP-2), and gluconeogenesis-related gene (G6Pase) are detected in groin adipose tissue and interscapular brown fat. In tissues, the expression of UCP1 gene, which is a marker of brown adipocyte activation, was analyzed.
In addition, the expression level of the MCP1 gene, which is an inflammation marker, was analyzed in all adipose tissues (groin adipose tissue, peritesticular adipose tissue, mesenteric adipose tissue, interscapular brown adipose tissue).
The 36B4 gene was used as an internal standard, and the following primers were used for analysis of the expression level of each gene.

SREBP1c-F; TCGCGGAGCCATGGATT (SEQ ID NO: 1)
SREBP1c-R; GCCAGGGAAGTCACTGTCTTG ((SEQ ID NO: 2))
FAS-F; GCAAATTCGACCTTTCTCAGAAC (SEQ ID NO: 3)
FAS-R; GGACCCCGTGGAAATTCA (SEQ ID NO: 4)
SCD1-F; TGTGGAGCCCACCCTCTTAC (SEQ ID NO: 5)
SCD1-R; ACGAGCCCATTCATAGACATCA (SEQ ID NO: 6 in the sequence listing)
G6Pase-F: TCGGAGACTGGTTCAACCTC (SEQ ID NO: 7)
G6Pase-R: TCACAGGTGACAGGGAACTG (SEQ ID NO: 8)
SREBP2-F: AAGTGACCGAGAGCTCCTTG (SEQ ID NO: 9)
SREBP2-R: ACGTTGAGAACTGCTCCCACAG (SEQ ID NO: 10)
UCP1-F: CCAAAGTCCCCCTCTAGA (SEQ ID NO: 11)
UCP1-R: GGCAATCCCTTCGTTTTTGC (SEQ ID NO: 12)
MCP1-F: CCACTCACCCTCGCTACTCAT (SEQ ID NO: 13)
MCP1-R: TGGTGATCCTCTTGTAGCTCTCC (SEQ ID NO: 14)
36B4-F: GGCCCTGCACTCTCGCTTC (SEQ ID NO: 15)
36B4-R: TGCCAGGACGCGCTTTGT (SEQ ID NO: 16 in the Sequence Listing)

2. Test results (1) Body weight, weight of each tissue, plasma parameters The results are shown in Table B1. In the Thermophilus group, body weight was significantly reduced compared to the control group.
In addition, the weight of the brown adipose tissue between the liver and the scapula is also significantly decreased, and the weight of the inguinal adipose tissue corresponding to subcutaneous fat and the weight of peritesticular adipose tissue and mesenteric adipose tissue corresponding to visceral fat are decreasing Indicated. In addition, plasma triglyceride levels were significantly reduced.

(2) Liver lipid The results are shown in Table B2. In the Thermophilus group, the total lipid and triglyceride concentrations in the liver tended to decrease compared to the control group.

　これらの結果から、ストレプトコッカス・サーモフィルスは、皮下脂肪や内臓脂肪の蓄積を抑制して肥満を防止するとともに、血中の中性脂肪を低下させ、肝臓への脂肪の蓄積を抑制することにより代謝を改善することが分かった。

From these results, Streptococcus thermophilus prevents the obesity by suppressing the accumulation of subcutaneous fat and visceral fat, reduces the neutral fat in the blood, and suppresses the accumulation of fat in the liver. Was found to improve.

(3) Metabolic improvement mechanism (i) Expression results of fatty acid synthesis-related genes, cholesterol synthesis-related genes, and gluconeogenesis-related genes in the liver are shown in Table B3. In the Thermophilus group, the expression of fatty acid synthesis-related genes, cholesterol synthesis-related genes, and gluconeogenesis-related genes in the liver was significantly reduced compared to the control group.

(ii) UCP1 gene expression The results are shown in Table B4. In the Thermophilus group, the expression of UCP1 gene, which is a marker of brown adipocyte activation, was significantly increased in interscapular brown adipose tissue as compared to the control group. Therefore, in the Thermophilus group, the expression of UCP1 gene per cell of interscapular brown adipose tissue was increased and fat burning was promoted, so that the weight of interscapular brown fat group was controlled as shown in Table B1. It was thought to have decreased compared to the group. In addition, in the groin adipose tissue, which is a white adipose tissue, the expression of UCP1 gene, which is a marker of brown adipocyte activation, markedly increased, so that some of the white adipose precursor cells differentiated into brown adipocytes. It was shown that

(iii) Expression of MCP1 gene The results are shown in Table B5. In the Thermophilus group, the expression of the MCP1 gene, which is a marker of inflammation in adipose tissue, was significantly reduced compared to the control group.

From these facts, Streptococcus thermophilus promotes the differentiation of white adipose precursor cells into brown adipocytes and also promotes activation of brown adipose tissue. It was also found that metabolic syndrome was improved by suppressing the expression of fatty acid synthesis-related genes, cholesterol synthesis-related genes, and gluconeogenesis-related genes in the liver, and further by suppressing inflammation of adipose tissue.

[Example B2] Production of composition for improving metabolism of adipocytes Centrifugation of Streptococcus thermophilus SBT1277 M17 medium (manufactured by OXOID) at 4 ° C. and 7000 rpm for 15 minutes, followed by washing with sterile water and centrifugation Separation was repeated 3 times to obtain washed cells. The washed cells were freeze-dried to obtain cell powder. This can be used as it is as a composition for improving metabolism of fat cells.
The viable cell count of Streptococcus thermophilus SBT1277 in the above composition was 1.6 × 10 ¹¹ cfu / g.

[Example B3] Manufacture of a drug for improving metabolism of fat cells 4 parts of skimmed milk powder was mixed with 1 part of the bacterial cell powder prepared in Example B2, and this mixed powder was tableted 1 g at a time by a conventional method. Thus, a tablet containing 200 mg of cells of Streptococcus thermophilus SBT1277 was prepared.

[Example B4] Production of fermented milk for improving adipocyte metabolism 10% reduced skim milk medium was sterilized at 115 ° C for 15 minutes, then inoculated with Streptococcus thermophilus SBT1277, cultured at 37 ° C for 16 hours, and skim milk Cultures were prepared. The skim milk culture was inoculated into a fermented mix (16% skim milk powder + 3% glucose) sterilized at 100 ° C. for 10 minutes and fermented at 39 ° C. for 10 hours to obtain fermented milk for improving fat cell metabolism.
The viable cell count of Streptococcus thermophilus SBT1277 in the fermented milk was 1.8 × 10 ⁹ cfu / g.

[Example B5] Production of lactic acid bacteria beverage for improving fat cell metabolism 10 g of fermented mix (16% nonfat dry milk + 3% glucose) obtained by sterilizing Streptococcus thermophilus SBT1277 cultured in 10% reduced nonfat milk medium at 95 ° C for 90 minutes It added so that it might become 3%, and it culture | cultivated at 35 degreeC for 20 hours. 10 g of this culture was mixed with 40 g of isomerized sugar (BRIX 15%) to obtain a lactic acid bacteria beverage for improving metabolism of fat cells.
The viable cell count of Streptococcus thermophilus SBT1277 in the lactic acid bacteria beverage was 4 × 10 ⁸ cfu / g.

[Example B6] Production of a composition for improving metabolism of fat cells A reduced skim milk medium (13% by weight skim milk powder, 0.5% yeast extract) was sterilized at 95 ° C for 30 minutes and then inoculated with Streptococcus thermophilus SBT1277. The resulting culture was centrifuged at 5000 rpm for 20 minutes to obtain a culture supernatant from which the precipitate was removed. This can be used as it is as a composition for improving metabolism of fat cells.

[Example B7] Production of health food for improving metabolism of adipocytes 50 g of the culture powder of Streptococcus thermophilus SBT1277 obtained in Example B1, 40 g of an equal mixture of vitamin C and citric acid, 100 g of granulated sugar, corn starch 60 g of an equal amount mixture of lactose and lactose was added and mixed. The mixture was packed in a stick-shaped bag to obtain a health food for improving fat cell metabolism.

[Example B8] Production of feed for improving metabolism of fat cells Soybean meal 12 kg, skim milk powder 14 kg, soybean oil 4 kg, corn oil 2 kg, palm oil 23.2 kg, corn starch 14 kg, wheat flour 9 kg, bran 2 kg, vitamin mixture 5 kg, Blended with 2.8 kg of cellulose and 2 kg of mineral mixture, sterilized at 120 ° C. for 4 minutes, blended with 10 kg of the culture powder of Streptococcus thermophilus SBT1277 obtained in Example B1, and feed for improving metabolism of fat cells Manufactured.

[Example B9] Production of hard natural cheese for improving metabolism of fat cells The raw milk was sterilized by heating (75 ° C, 15 seconds), cooled to 30 ° C, and 0.01% calcium chloride was added. Furthermore, 0.7% of commercially available lactic acid bacteria starter (LD starter, Christian Hansen) and 1% of Streptococcus thermophilus SBT1277 were added, and 0.003% of rennet was further added to coagulate the milk. The curd thus obtained was cut and stirred until the pH was 6.2 to 6.1, and the whey was discharged to obtain curd grains. Then, the curd grains were molded, pressed, further salted and aged at 10 ° C. to produce Gouda cheese type hard natural cheese for improving fat cell metabolism containing Streptococcus thermophilus SBT1277.

As a new solution for improving lipid metabolism, the first invention is a composition for improving lipid metabolism comprising a lactic acid bacterium belonging to Streptococcus thermophilus as an active ingredient, a food for improving lipid metabolism, a pharmaceutical comprising the composition, And providing feed.
Therefore, improvement of lipid metabolism can be expected in a simple and safe manner by ingesting the above composition, food, medicine and feed of the present invention.

The second invention comprises a composition for improving metabolism of adipocytes, such as promotion of differentiation from white adipose precursor cells to brown adipocytes, activation of brown adipocytes, comprising lactic acid bacteria belonging to Streptococcus thermophilus as an active ingredient, and Food for improving metabolism of adipocytes, pharmaceutical and feed containing the composition, composition for improving metabolic syndrome containing lactic acid bacteria belonging to Streptococcus thermophilus as an active ingredient, and food for improving metabolic syndrome and pharmaceutical containing the composition And providing feed.
According to the present invention, improvement of adipocyte metabolism and metabolic syndrome can be expected in an easy and safe manner by ingesting the above composition, food, medicine and feed.

(Trust number)
FERM BP-3234
FERM P-9442
FERM P-9443
FERM P-10658
FERM P-16638
FERM P-19531
NITE P-02398

[Reference to deposited biological materials]
(1) SBT1277
(I) Name and address of the depositary institution that deposited the biological material Patent Evaluation Microorganisms Depositary Center, Patent Evaluation Microorganisms Center 2-5-2, Kazusa Kamashi, Kisarazu City, Chiba Prefecture, Japan (zip code 292-0818)
Date of deposit of biological materials at Loi depository December 11, 2001 (original deposit date)
January 22, 1991 (Date of transfer to deposit under the Budapest Treaty by original deposit)
Deposit number FERM BP-3234 assigned by the depository in Thailand for deposit
(2) SBT0104
(I) Name and address of the depositary institution that deposited the biological material Patent Evaluation Microorganisms Depositary Center, Patent Evaluation Microorganisms Center 2-5-2, Kazusa Kamashi, Kisarazu City, Chiba Prefecture, Japan (zip code 292-0818)
Date of deposit of biological materials at Loi depository organization June 30, 1987 (original deposit date)
Deposit number FERM P-9442 attached to the depository by the depository in Hai
(3) SBT0113
(I) Name and address of the depositary institution that deposited the biological material Patent Evaluation Microorganisms Depositary Center, Patent Evaluation Microorganisms Center 2-5-2, Kazusa Kamashi, Kisarazu City, Chiba Prefecture, Japan (zip code 292-0818)
Date of deposit of biological materials at Loi depository organization June 30, 1987 (original deposit date)
Deposit number FERM P-9443 assigned by the depository in Thailand
(4) SBT1021A
(I) Name and address of the depositary institution that deposited the biological material Patent Evaluation Microorganisms Depositary Center, Patent Evaluation Microorganisms Center 2-5-2, Kazusa Kamashi, Kisarazu City, Chiba Prefecture, Japan (zip code 292-0818)
Date of deposit of biological materials at Loi depository April 13, 2001 (original deposit date)
Deposit number FERM P-10658 attached to the depositary by the high depository
(5) SBT0144
(I) Name and address of the depositary institution that deposited the biological material Patent Evaluation Microorganisms Depositary Center, Patent Evaluation Microorganisms Center 2-5-2, Kazusa Kamashi, Kisarazu City, Chiba Prefecture, Japan (zip code 292-0818)
Date of deposit of biological materials at Loi depository February 17, 1998 (original deposit date)
Deposit number FERM P-16638 assigned by the depository in Thailand
(6) SBT10137
(I) Name and address of the depositary institution that deposited the biological material Patent Evaluation Microorganisms Depositary Center, Patent Evaluation Microorganisms Center 2-5-2, Kazusa Kamashi, Kisarazu City, Chiba Prefecture, Japan (zip code 292-0818)
Date of deposit of biological materials at Loi depository, September 25, 2003 (original deposit date)
Deposit number FERM P-19531 assigned by the depository in Thailand
(7) SBT1063
(I) Name and address of the depositary institution that deposited the biological material Patent Evaluation Microorganisms Depositary Center, Patent Evaluation Microorganisms Center 2-5-2, Kazusa Kamashi, Kisarazu City, Chiba Prefecture, Japan (zip code 292-0818)
Date of deposit of biological materials at Loi depository organization December 27, 2016 (original deposit date)
(In addition, after the original deposit date, an application was made for transfer to deposit under the Budapest Treaty based on the original deposit, and after completion of the survival confirmation test, a document notifying the receipt / acceptance number was received. 02398.)
Deposit number NITE P-02398 assigned by the depository in Hai

Claims (16)

A composition for improving lipid metabolism comprising a culture of lactic acid bacteria and / or bacterial cells belonging to Streptococcus thermophilus. The composition for improving lipid metabolism according to claim 1, wherein the lactic acid bacterium belonging to Streptococcus thermophilus is any one of Streptococcus thermophilus SBT1277 (FERM BP-3234) and SBT1063 (NITE P-02398). The composition for improving lipid metabolism according to claim 1 or 2, wherein the lipid metabolism is lipid metabolism in the liver. A food for improving lipid metabolism comprising the composition for improving lipid metabolism according to claim 3. A lipid metabolism-improving pharmaceutical comprising the lipid metabolism-improving composition according to claim 1. A feed for improving lipid metabolism comprising the composition for improving lipid metabolism according to claim 3. Streptococcus thermophilus SBT-1063 (NITE P-02398), which is a novel lactic acid bacterium belonging to Streptococcus thermophilus. A composition for improving lipid metabolism,
Including a culture and / or cells of lactic acid bacteria to make Streptococcus thermophilus,
A composition for improving lipid metabolism that promotes differentiation of white fat precursor cells into brown fat cells. The composition for improving lipid metabolism according to claim 8, wherein the lactic acid bacterium belonging to Streptococcus thermophilus is Streptococcus thermophilus SBT1277 (FERM BP-3234). A composition for activating brown adipocytes containing a culture of lactic acid bacteria and / or bacterial cells belonging to Streptococcus thermophilus. The composition for activating brown adipocytes according to claim 10, wherein the lactic acid bacterium belonging to Streptococcus thermophilus is Streptococcus thermophilus SBT1277 (FERM BP-3234). A composition for improving metabolic syndrome, comprising a culture of lactic acid bacteria and / or cells belonging to Streptococcus thermophilus. The composition for improving metabolic syndrome according to claim 12, wherein the lactic acid bacterium belonging to Streptococcus thermophilus is Streptococcus thermophilus SBT1277 (FERM BP-3234). A food, medicine or feed for promoting differentiation from white adipose precursor cells to brown adipocytes, comprising the composition for improving lipid metabolism according to claim 8 or 9. A food, medicine or feed for activating brown adipocytes comprising the composition for activating brown adipocytes according to claim 10 or 11. A food, medicine or feed for improving metabolic syndrome comprising the composition for improving metabolic syndrome according to claim 12 or 13.