JP2007284360A - Composition for activating ppar-dependent gene transcription, originated from lactobacillus - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a composition which improves lipid metabolism by the activation of a peroxisome proliferator-activated receptor (PPAR), is used for treating, preventing or improving diabetes, hyperlipemia and abesity, and is highly safe. <P>SOLUTION: This composition used for inducing the expression of a lipid β-oxidase group by the activation of PPAR to improve lipid metabolisms, and for treating, preventing or improving obesity and the like contains, as an active ingredient, an organic solvent extract of one or more lactobacilli selected from lactobacilli belonging to the genus Lactobacillus such as Lactobacillus helveticus ATCC1120, Lactobacillus amylovorus ATCC33620, Lactobacillus pentosus ATCC8041, Lactobacillus curvatus ATCC25601, Lactobacillus gasseri ATCC33323, Lactobacillus reuteri ATCC23272, Lactobacillus fructivorans NCI9040, and Lactobacillus acetotolerans ATCC43578. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention provides treatment, prevention, or activation by activation of a peroxisome proliferator-activated receptor (hereinafter also referred to as PPAR), which comprises an organic solvent extract of lactic acid bacteria as an active ingredient. More particularly, the present invention relates to a composition for use in the treatment, prevention, or amelioration of a disease or symptom that can be ameliorated, and more particularly, the activation of PPAR comprising an organic solvent extract of lactic acid bacteria as an active ingredient. Promotes transcription, especially promotes gene expression of β-oxidation-related enzymes important for fatty acid metabolism, improves fat burning function in the body to prevent fat accumulation, obesity and obesity-induced diabetes, hypertension, Provide a composition that can treat, prevent or ameliorate hyperlipidemia, etc. Is shall.

  Obesity is a condition in which body fat has accumulated excessively, and is often caused by lifestyle habits such as excessive intake of nutrients and lack of exercise. Obesity is the onset of many lifestyle-related diseases such as diabetes, hypertension, and hyperlipidemia. It is said to be the foundation and has become a social problem.

  The basis for combating obesity is diet therapy and exercise therapy. When it is difficult to apply these therapies for various reasons, drug therapy using anti-obesity drugs or the like is performed.

  Currently, some drugs used as anti-obesity drugs have the effect of activating PPAR, one of the factors that promote gene expression of β-oxidation-related enzymes, which play an important role in the fat burning system. Chemically synthesized drugs are known, for example, fibrates such as fenofibrate and bezafibrate. However, it is necessary to continue treatment with these chemically synthesized drugs over a long period of time, and there are problems such as accompanying side effects.

  Therefore, while the risk of side effects is low and excellent safety is expected, catechins, humulones, isohumulones, or luprones have recently been disclosed as components derived from natural products that activate PPAR. Yes. However, the effects of activating PPARs derived from these natural products and food materials, and the effects of preventing, treating and improving obesity have not been fully satisfactory.

  On the other hand, lactic acid bacteria that have been used in the food field since ancient times and are highly safe fermenting microorganisms, for example, prevent obesity by orally ingesting Lactobacillus fermentum that produces polysaccharide substances. A therapeutic preparation (Patent Document 1), a composition for preventing visceral fat accumulation or a food (Patent Document 2) containing a lactic acid bacteria culture or the like as an active ingredient are disclosed.

  However, these lactic acid bacteria utilization techniques are intended to utilize the activity of lactic acid bacteria in the human body such as the intestines and enzymes produced by lactic acid bacteria, and do not utilize the action of activating PPAR. The substance extracted from was not used.

Therefore, it has been demanded to develop a highly safe substance that has a stronger effect of activating PPAR and has a stronger effect of preventing, treating, or improving obesity.
JP 2005-40123 A Japanese Patent Laid-Open No. 10-298083

  The present invention is highly safe, has a strong PPAR activation action, promotes the transcriptional activity of PPAR-dependent genes, particularly promotes gene expression of β-oxidation-related enzymes important for fatty acid metabolism, It is intended to provide a composition capable of improving fat burning function to prevent fat accumulation and treating, preventing or improving diabetes, hypertension, hyperlipidemia and the like induced by obesity and obesity state.

  In order to find a substance having a strong PPAR activation action with a high safety and a low risk of side effects, and thus a strong fat burning effect, a substance having a stronger anti-obesity, treatment and improvement action, A wide range of searches were conducted for existing objects.

  As a result, paying attention to lactic acid bacteria that have dietary experience in the form of various fermented foods, and further examining their processed products, they found for the first time that the organic solvent extract has the above-mentioned activity and led to the completion of the present invention. It is.

  That is, the present invention is characterized in that an organic solvent extract of lactic acid bacteria is used as an active ingredient, and the following modes are exemplified.

(1) Treatment of a disease or symptom that can be treated, prevented, or ameliorated by activating a peroxisome proliferator-responsive receptor, comprising an organic solvent extract of lactic acid bacteria as an active ingredient, or A composition for prevention or improvement.

(2) The composition according to (1) above, wherein the disease or symptom that can be treated, prevented, or ameliorated by activation of a peroxisome proliferator-responsive receptor is obesity.

(3) Lactic acid bacteria are Lactobacillus helveticus, Lactobacillus amylovorus, Lactobacillus pentosus, Lactobacillus pentosus, Lactobacillus pentosus ), Lactobacillus reuteri, Lactobacillus fructivorans, Lactobacillus acetotolerans Or the composition as described in said (1) or (2) characterized by being 2 or more types.

(4) Lactobacillus strains Lactobacillus helveticus ATCC1120 (Lactobacillus helveticus ATCC1120) strain, Lactobacillus amylovorus ATCC33620 (Lactobacillus amylovus ATCC33620) strain, Lactobacillus amyltocus AT41 curvatus ATCC 25601) strain, Lactobacillus gazeri ATCC 33323 (Lactobacillus gasseri ATCC 33323) strain, Lactobacillus reuteri ATCC 23272 (Lactobacillus) reuteri ATCC23272) strain, Lactobacillus fructivorans NCI9040 (Lactobacillus fructivarans NCI9040) strain (FERM BP-10482), Lactobacillus acetotolerans strain ATCC 43578 (Lactobacillus aceto4 strain) The composition according to any one of (1) to (3) above.

(5) The composition according to any one of (1) to (4) above, which is a food or drink.

(6) The composition according to any one of the above (1) to (5), which is designed so that 1 to 30 g of an organic solvent extract derived from lactic acid bacteria can be ingested per day. .

(7) The organic solvent extract of lactic acid bacteria is added to the dried cells of lactic acid bacteria, the supernatant after homogenizer treatment or ultrasonic crushing is concentrated to dryness, and the organic solvent is added to the dried solids. The composition according to any one of (1) to (6) above, which is light yellow, insoluble in water, and has no viscosity.

(8) The composition according to (7) above, wherein the dried lactic acid bacteria are a mixture of two or more lactic acid bacteria.

  According to the present invention, by ingesting an organic solvent extract of lactic acid bacteria, PPAR activation is enhanced, gene expression of liver β-oxidation-related enzymes is promoted, lipid metabolism is promoted, and obesity is prevented. It is possible to provide a composition that can be treated and improved, and further can prevent, treat and ameliorate lifestyle-related diseases such as diabetes, hypertension and hyperlipidemia induced by obesity.

  Hereinafter, the present invention will be described in detail.

  As the lactic acid bacterium used in the present invention, any lactic acid bacterium can be used as long as it can provide an extract having PPAR activation ability. Among them, from the viewpoint of safety, it belongs to the genus Lactobacillus. Lactic acid bacteria are desirable.

  For example, Lactobacillus helveticus, Lactobacillus amiloborus, Lactobacillus pentosus, Lactobacillus genus, Lactobacillus pentosus -Reuteri (Lactobacillus reuteri), Lactobacillus fructivorans (Lactobacillus frutivorans), Lactobacillus acetotolerans (Lactobacillus acetotolerans), etc. However, Lactobacillus amylovorus, Lactobacillus fructivorans and Lactobacillus acetotolerans are highly effective and suitable.

  More specifically, Lactobacillus helveticus ATCC1120 (Lactobacillus helveticus ATCC1120) strain, Lactobacillus amylovorus ATCC33620 (Lactobacillus amylovorus ATCC33620) strain, Lactobacillus amyltocus AT41 curvatus ATCC25601) strain, Lactobacillus gazeri ATCC33323 (Lactobacillus gasseri ATCC33323) strain, Lactobacillus reuteri ATCC23272 (Lactobacillus) reuteri ATCC23272) strain, Lactobacillus Furukuchiboransu NCI9040 (Lactobacillus fructivorans NCI9040) strain, Lactobacillus acetoacetate tolerance NCIATCC43578 (Lactobacillus acetotolerans ATCC43578) strain and the like, and among them, Lactobacillus Amiroborusu ATCC33620 (Lactobacillus amylovorus ATCC33620) strain, Lactobacillus -Fructivolans NCI9040 (Lactobacillus flutivorans NCI9040) strain and Lactobacillus acetotolerance ATCC 43578 (Lactobacillus acetotol) rans ATCC43578) are those strains are preferred.

  Among these lactic acid bacterial strains, those with ATCC numbers are stored in the ATCC (American Type Culture Collection) and can be transferred, and also Lactobacillus fructivorans NCI9040 (Lactobacillus fultivorans). NCI9040) was deposited on December 27, 2005 at the National Institute of Advanced Industrial Science and Technology, Patent Biological Depositary Center (1st, 1st East, 1st Street, Tsukuba City, Ibaraki Prefecture) on December 27, 2005. BP-10421.

  As a method for culturing these microorganisms, any method such as a liquid culture method or a solid culture method may be used as long as it is a commonly used method. That is, any of a synthetic medium or a natural medium containing an appropriate ratio of a carbon source, a nitrogen source, an inorganic substance, and other nutrients suitable for the microorganism to be cultured can be used. This is cultured under arbitrary culture conditions and collected by a centrifugal separator.

  The collected lactic acid bacteria are extracted with a polar solvent to obtain an extract. The term “extraction” as used herein means an extract obtained by extracting lactic acid bacteria with a polar solvent, a diluted solution, a concentrated solution, an extract, a dried product obtained by drying the extract, and a separated and purified compound.

  Here, the polar solvent means alcohols such as methanol, ethanol, 1-propanol, 2-propanol and 1-butanol, ethers such as 1,4-dioxane, ketones such as acetone, and nitriles such as acetonitrile. Preferably, lower alcohols such as methanol and ethanol are used.

  As the extract, any polar solvent extract of lactic acid bacteria can be widely used. For example, the extract can be produced as follows. First, a polar solvent is added to the collected lactic acid bacteria, and the mixture is stirred at 0 ° C. to room temperature (for example, 15 to 35 ° C.) for 10 to 90 minutes, preferably 30 to 60 minutes, and filtered or centrifuged as necessary. An insoluble matter is removed by the operation, and the solvent is removed and concentrated to obtain a lactic acid bacteria organic solvent extract. In addition, the lactic acid bacterial cells may be subjected to extraction with a polar solvent without being crushed, or the crushed bacterial cells may be subjected to an extraction treatment or may be extracted while being crushed. As the crushing treatment, a conventional method of crushing microbial cells is used as appropriate, such as grinding with a mortar or the like, ultrasonic treatment, homogenizer treatment, or the like.

  More specifically, an organic solvent extract of lactic acid bacteria can be produced as follows. First, after culturing lactic acid bacteria, the culture solution is subjected to solid-liquid separation treatment such as centrifugation, and collected and freeze-dried.

  1 to 10 ml, preferably 2 to 8 ml of an organic solvent (ethanol, methanol, propanol, etc.) is added to 1 g of dried cells and treated with an ultrasonic crusher for 0.5 to 5 minutes, followed by ultrasonic crushing. If desired, other means can be used as long as the cells can be disrupted. Next, the supernatant is recovered by solid-liquid separation. For example, it may be centrifuged at 5,000 to 10,000 × g, 4 ° C. for 5 to 30 minutes. Since this treatment is performed for the purpose of separating and recovering the supernatant, the conditions for centrifugation may be appropriately determined within the above range. In some cases, it may deviate from the above range. Various known solid-liquid separation processes such as filtration other than centrifugation are also possible. The resulting supernatant is evaporated to dryness. If desired, 0.1 to 5 ml, preferably 0.5 to 2 ml of an organic solvent may be added to the dried product, and this may be used as an organic solvent extract of lactic acid bacteria.

  The composition of the present invention contains an organic solvent extract of lactic acid bacteria as an active ingredient and is used as a pharmaceutical, as well as normal foods and drinks, functional foods, foods for specific health and health aids. It can also be used as food. Therefore, the present invention can be said to be a use invention related to a specific use.

  The form of the composition according to the present invention is not particularly limited. For example, when used as a medicine (for example, anti-obesity agent, anti-diabetic agent, anti-hyperlipidemic agent, diet agent, PPAR activator, etc.), oral It can be administered as an administration agent or a parenteral administration agent (for example, an intravenous injection such as an emulsion or injection).

  Oral administration agents are the same for pharmaceuticals and foods and drinks, but oral solid preparations such as tablets, granules, fine granules, sticks, capsules, troches, and oral preparations such as syrups A liquid agent etc. may be sufficient. In the case of food, it may be a drink. In the case of pharmaceuticals, parenteral agents, for example, intravenous injections such as emulsions and injections may be used, and various excipients, carrier agents such as preservatives and solvents can be used depending on the type of composition. If necessary, other physiologically active ingredients can be used in combination.

  In addition, in the case of a food or drink, for example, a label indicating that the peroxisome proliferator-responsive receptor (PPAR) has an activation function or a label indicating that it has a fat burning effect is added. Indicates that a disease or condition that can be treated, prevented, or ameliorated by activation of peroxisome proliferator-activated receptor (PPAR), such as obesity, diabetes, hyperlipidemia, etc., is treated, prevented, or ameliorated. Foods for specified health use (health foods).

The dose or intake of the active ingredient according to the present invention may be determined depending on the recipient's sex, age, weight, and symptoms and administration time, dosage form, administration method, combination of drugs, etc. It is preferable to administer an organic solvent extract extracted from 1 to 30 g of lactic acid bacteria per person per day, and more preferably 10 to 30 g of lactic acid bacteria can be ingested.
In this case, the number of intakes per day does not have to be limited to one, and the intake can be divided into several times during the day.

  Incidentally, in this invention, the effect was seen by administering the organic-solvent extract extracted from 0.1-0.3g lactic acid bacteria in the mouse | mouth. When this result is converted into a human, a method of 10 to 100 times is generally adopted, and therefore an organic solvent extract extracted from 1 to 30 g of lactic acid bacteria per person per day is preferably 10 to 100 times. It is considered effective by ingesting an organic solvent extract extracted from 30 g of lactic acid bacteria. Since the active ingredient of the composition according to the present invention is a natural product and derived from a lactic acid bacterium that has a dietary experience, there is no particular problem in safety, and as a result of a 10-day acute toxicity test using mice, No death occurred even after oral administration of 1000 mg / Kg.

  Hereinafter, the present invention will be described in more detail with reference to examples and the like, but the present invention is not limited to these examples.

(Example 1) Production of an organic solvent extract of lactic acid bacteria 5 ml of MRS medium (per liter, 10.0 g of polypeptone, 8.0 g of meat extract, 4.0 g of yeast extract, 20 g of glucose, 1.0 g of “Tween 80”, Autoclaving dipotassium hydrogen phosphate 2.0 g, diammonium hydrogen citrate 2.0 g, sodium acetate trihydrate 5.0 g, magnesium sulfate heptahydrate 0.2 g, manganese sulfate tetrahydrate 0.05 g) Sterilized at 121 ° C. for 15 minutes, each lactic acid bacterium shown in Table 1 was inoculated and cultured at 30 ° C. for 12 hours. This whole amount was added to 500 ml of MRS medium and further cultured at 30 ° C. for 24 hours.

  In addition, Lactobacillus fructivorans NCI9040 (Lactobacillus fructivorans NCI9040) strains in Table 1 are registered in the National Institute of Advanced Industrial Science and Technology Patent Biological Depositary Center (1st, 1st, 1st East, 1-chome, Tsukuba, Ibaraki Prefecture) December 2005 It has been deposited on the 27th, and its deposit number is FERM BP-10481.

  After completion of the culture, 500 ml of the culture solution was collected by centrifugation (7500 × g, 4 ° C., 15 minutes), and freeze-dried. Table 2 shows the dry cell weight per 500 ml culture of each lactic acid bacterium obtained.

Add 5 ml of ethanol to a 15 ml test tube containing 1 g of these dry cells, and use an ultrasonic crusher (Branson Sonifier 450) for 2 minutes under conditions of Output control: 7 and Duty cycle: 60%. Sonication was performed. This was centrifuged again (7500 × g, 4 ° C., 15 minutes) to recover the supernatant. The resulting supernatant was concentrated to dryness using a rotary evaporator, and 1 ml of ethanol was added to the dried product. An extract of lactic acid bacteria was obtained.
The obtained extract was light yellow, insoluble in water and fat-soluble, and was not viscous.

(Example 2) Test of PPAR-dependent gene transcription activity Human liver cancer-derived cells HepG2 are plated on 24-well plates and cultured in DMEM containing 5% FBS for 24 hours.

  On the other hand, a DNA chain containing a repetitive sequence of a PPAR response element (PPAR response element) TGACCTTTGTBBT was inserted into a reporter vector pGL3-promoter vector (Promega) containing an SV40 promoter gene and a firefly luciferase gene. The above plasmid was transfected into HepG2 cells together with the Renilla luciferase reporter vector pRL-TK Vector, which is a control plasmid, using Fugene 6 (Roche Diagnostics).

Twelve hours after transfection, the culture medium was replaced with D-MEM (5% FBS) containing a test substance, and further incubated at 37 ° C. and 5% CO _{2 for} 24 hours.

  After the incubation, the cells are washed with PBS, and then collected. The cells are lysed using Dual-Luciferase Reporter Assay System (Promega), a substrate solution containing luciferin is added to the lysate, and firefly luciferase and renilla luciferase are added. Activity was measured with a luminometer. The value obtained by dividing the firefly luciferase activity by the Renilla luciferase activity was defined as the luciferase activity value.

  Table 3 shows the PPAR-dependent gene transcription activity ability of each test substance in HepG2. The results are expressed as relative activity values when the negative control value is 1. As a positive control, ciprofibrate was used.

  From the results in Table 3, Lactobacillus helveticus ATCC1120 (Lactobacillus helveticus ATCC1120) strain, Lactobacillus amylovorus ATCC33620 (Lactobacillus amylovorus ATCC33620) strain, Lactobacillus amylocus Lactococ L41 curvatus ATCC 25601) strain, Lactobacillus gazeri ATCC 33323 (Lactobacillus gasseri ATCC 33323) strain, Lactobacillus reuteri ATCC 23272 (Lactobacillus) reuteri ATCC23272) strain, Lactobacillus fructivorans NCI9040 (Lactobacillus fructivorans NCI9040) strain, Lactobacillus acetotolerans ATCC 43578 (Lactobacillus acetotolerans ATCC 43578) -dependent lactic acid-derived lactic acid-derived lactic acid product-dependent strains

  Among them, Lactobacillus amylobolus ATCC 33620 (Lactobacillus amylovorus ATCC 33620) strain, Lactobacillus fructivorans NCI9040 (Lactobacillus fructovivorans NCI9040) strain, Lactobacillus fructoviolans NCI9040 strain, It was confirmed that the activity was stronger than that of the positive control group using ciprofibrate).

(Example 3) Effect on body weight gain and energy efficiency (1) Effect by administration of dried lactic acid bacteria The administration effect of dried lactic acid bacteria was tested under the following test conditions.

  First, three types of lactic acid strains shown in Table 5 were cultured by the following methods. That is, 5 ml of MRS medium was sterilized in an autoclave at 121 ° C. for 15 minutes, inoculated with each lactic acid strain, and cultured at 30 ° C. for 12 hours. Thereafter, the total amount of each culture solution was added to 500 ml of MRS medium, and further cultured at 30 ° C. for 24 hours. Further, the total amount of each culture solution was added to 10 liters of MRS medium, and further cultured at 30 ° C. for 48 hours.

  After completion of the culture, each culture solution was centrifuged (7500 × g, 4 ° C., 15 minutes) and collected. Then, after suspending these in 2 liters of water, the dry microbial cell of each lactic acid bacteria was obtained by freeze-drying.

<Test conditions>
(Animal used) 4 weeks old, KKAy / Ta Jcl mouse female (Claire Japan)
(Feed / Water) AIN-93G purified feed (powder) shown in Table 4 and water were freely ingested and acclimated for 1 week. The test feed was fed freely and the drinking water was tap water. In Table 4, the composition of Mineral Mixture AIN93G and Vitamin Mixture AIN93G marked with * is “Journal of Nutrition (J. Nutr.)”, Vol. 123, p. 1939-951, 1993.

  (Experimental group) A group fed with AIN-93G (control group, n = 5) and a group fed with 5% by weight of the dried lactic acid bacteria shown in Table 5 (dried lactic acid bacteria) Groups, n = 5) were set up.

  The results are shown in Table 6.

  In the result of Table 6, even if it ingested lactic-acid-bacteria dried material, the significant effect was not seen regarding a body weight or energy efficiency.

(2) Effect of administration of lactic acid bacteria extract The administration effect of lactic acid bacteria extract was tested under the following test conditions.

  First, three types of lactic acid strains shown in Table 7 were cultured by the following methods. That is, 5 ml of MRS medium was sterilized in an autoclave at 121 ° C. for 15 minutes, inoculated with each lactic acid strain, and cultured at 30 ° C. for 12 hours. Thereafter, the total amount of each culture solution was added to 500 ml of MRS medium, respectively, and further cultured at 30 ° C. for 24 hours. Further, each culture solution was added to 10 liters of MRS medium and cultured at 30 ° C. for 48 hours.

  After completion of the culture, each culture solution was centrifuged (7500 × g, 4 ° C., 15 minutes) and collected. Thereafter, the collected bacterial cells were suspended in 2 liters of water and then freeze-dried to obtain dried lactic acid bacteria.

The obtained dried product of each lactic acid bacterium was mixed at a mixing ratio shown in Table 7, ethanol having a weight 10 times the total cell weight was added, and the mixture was stirred and extracted with a hogenizer. This was centrifuged again (7500 × g, 4 ° C., 15 minutes) to recover the supernatant. The resulting supernatant was concentrated to dryness with a rotary evaporator, and 10 ml of ethanol was added to the dried product to give lactic acid bacteria. An extract was obtained.
The obtained extract was light yellow, insoluble in water and fat-soluble, and was not viscous.

<Test conditions>
(Animal used) 4 weeks old, KKAy / Ta Jcl mouse female (Claire Japan)
Feed / water: AIN-93G purified feed (powder) shown in Table 4 and water were freely ingested and acclimated for 1 week. The test feed was fed freely and the drinking water was tap water.

  (Experimental group) AIN-93G fed with AIN-93G (control group, n = 5) and AIN-93G supplemented with 3% by weight of the lactic acid bacteria extract prepared at the mixing ratio shown in Table 7 The lactic acid bacteria ethanol extract group (n = 5) was set.

  The above results are shown in Table 8.

  As a result of the above, no significant difference was observed in the body weight by ingesting the lactic acid bacteria extract, but a significant decrease in energy efficiency was observed, confirming the effect of preventing obesity.

(Example 4) Expression promotion of β-oxidase gene by lactic acid bacteria extract The analysis was performed by the following method.

<Test conditions>
(Animal used) 4 weeks old, KKAy / Ta Jcl mouse female (Claire Japan)
Feed / water: AIN-93G purified feed (powder) shown in Table 4 and water were freely ingested and acclimated for 1 week. The test feed was fed freely and the drinking water was tap water.

  (Experimental group) A group fed with AIN-93G (control group, n = 5) and a group fed with 3% by weight of the lactic acid bacteria extract prepared in Example 3 (extracted with lactic acid bacteria) Group of objects, n = 5) was set.

<Analysis conditions>
Collection from the liver: After feeding the test feed for 4 weeks, mice fasted for 5 hours were immediately decapitated under ether anesthesia and blood was collected by decapitation. After further laparotomy, the liver was collected, weighed, frozen in liquid nitrogen and stored at -80 ° C. In addition, a part of the liver tissue was immediately stored in RNAlater (Ambion) for gene analysis.

  Collection of RNA from liver and measurement of liver β-oxidation gene expression: total RNA was purified using Rneasy (manufactured by QIAGEN). After measuring the amount of RNA using a spectrophotometer, cDNA was obtained using Taqman Reverse Transfer reagent (manufactured by Applied Bio Systems). For the obtained cDNA, Mm00443579 m1 (Applied Bio Systems) was used for ACO and Mm00431611 m1 (Applied BioSystems) was used for MCAD as the TaqMan probe. As an internal standard gene, acid ribosomal phosphoprotein P0 (acid ribosomal protein 36B4) gene Mm01974474 gH (manufactured by Applied Bio Systems) was used. TaqMan PCR was amplified and detected using PRISM7000 manufactured by Applied Bio Systems.

  In the above experiment, the expression levels of β-oxidase, such as acyl-CoA oxidase (ACO) mRNA and medium-chain acyl-CoA dehydrogenase (MCAD) mRNA, were analyzed, and the results are shown in Table 9.

  In addition, * in a table | surface shows that the significant difference was recognized by the risk rate P <0.01 with respect to the control group as a result of the significant difference test.

  As a result, it was confirmed that ingestion of lactic acid bacteria extract significantly induced β-oxidase gene expression by liver lactic acid bacteria extract, and it was confirmed that lipid metabolism could be activated. It was.

Claims (9)

  Treatment or prevention of a disease or symptom that can be treated, prevented, or ameliorated by activation of a peroxisome proliferator-responsive receptor, comprising an organic solvent extract of lactic acid bacteria as an active ingredient, or Composition for improvement.   The composition according to claim 1, wherein the disease or condition that can be treated, prevented, or ameliorated by activation of a peroxisome proliferator-responsive receptor is obesity.   Lactic acid bacteria include Lactobacillus helveticus, Lactobacillus amylovorus, Lactobacillus pentosus, Lactobacillus pentosus, Lactobacillus pentosus, Lactobacillus pentosus, Lactobacillus pentosus One or two selected from Lactobacillus reuteri, Lactobacillus fultivorans, Lactobacillus acetotolerans The composition according to claim 1, wherein the composition is a seed or more.   Lactic acid bacteria, Lactobacillus helveticus ATCC1120 (Lactobacillus helveticus ATCC1120) strain, Lactobacillus Amiroborusu ATCC33620 (Lactobacillus amylovorus ATCC33620) strain, Lactobacillus pentosus ATCC8041 (Lactobacillus pentosus ATCC8041) strain, Lactobacillus Kurubatasu ATCC25601 (Lactobacillus curvatus ATCC25601) Strain, Lactobacillus gazeri ATCC33323 (Lactobacillus gasseri ATCC33323) strain, Lactobacillus reuteri ATCC23272 (Lactobacillus reu) Teri ATCC23272) strain, Lactobacillus fructivorans NCI9040 (Lactobacillus frutivorans NCI9040) strain (FERM BP-10481), Lactobacillus acetotolerans ATCC 43578 (Lactobacillus acetotoleran strain ATCC The composition according to any one of claims 1 to 3.   It is food-drinks, The composition of any one of Claims 1-4 characterized by the above-mentioned.   The composition according to any one of claims 1 to 5, which is designed to be able to ingest 1 to 30 g of an organic solvent extract derived from lactic acid bacteria per day.   An organic solvent extract of lactic acid bacteria is obtained by adding an organic solvent to dry cells of lactic acid bacteria, concentrating and drying the supernatant after ultrasonic crushing, and adding an organic solvent to the dried product, which is pale yellow The composition according to claim 1, which is insoluble in water and has no viscosity.   8. The composition according to claim 7, wherein the dried lactic acid bacteria are a mixture of two or more lactic acid bacteria.   The organic solvent extract of lactic acid bacteria is added with 1 to 10 ml of organic solvent (at least one selected from methanol, ethanol, propanol) to 1 g of dried lactic acid bacteria, and subjected to ultrasonic crushing treatment for 0.5 to 5 minutes. The obtained supernatant is evaporated to dryness by a rotary evaporator, and 0.1 to 5 ml of the organic solvent is added to the dried product. The composition according to any one of claims 1 to 8, wherein the composition is.