JP2014185088A - Oral composition, adipocyte differentiation inhibitor, and food and drink - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an oral composition which can inhibit adipocyte differentiation, an adipocyte differentiation inhibitor, and food comprising them.SOLUTION: The oral composition for inhibiting adipocyte differentiation of the invention can inhibit adipocyte differentiation due to containing γ-oryzanol, can prevent obesity and improve physical constitution tend to break down fat to promote body weight loss by inhibiting increase in hypertrophy fat cells and increasing abundance ratio of a small fat cell, and can be optimally used as dietetic food, cosmetic food, food for exercise therapy, obesity diet, or the like.

Description

  The present invention relates to an oral composition for suppressing adipocyte differentiation, an adipocyte differentiation inhibitor, and a food or drink.

  In recent years, lifestyle-related diseases such as diabetes, hypertension, and hyperlipidemia have become a major social problem. In addition, accumulation of these lifestyle-related diseases and obesity with visceral fat accumulation (visceral obesity) has been shown to cause the onset of arteriosclerotic diseases. It is called. Japanese people are more affected by metabolic syndrome than Americans, and a specific screening system has been introduced since 2008, and it has been well known that visceral obesity is a significant risk factor for the development of lifestyle-related diseases.

  Obesity is an excessive amount of body fat, and this state is thought to involve the enlargement of the fat cells themselves and the increase in the number of fat cells. Today, there are a great many people who suffer from weight gain and body shape changes due to life work reasons such as overeating, uneven eating and lack of exercise. Therefore, it is highly desired to maintain beauty and health by suppressing body weight gain and body shape change by a simple and effective method. Usually, it is considered that mature adipocytes are involved in extreme changes in body weight and body shape.

  Mature adipocytes are differentiated preadipocytes and are roughly classified into so-called “small adipocytes” and “hypertrophic adipocytes” depending on their morphology. From another point of view, it is broadly divided into “brown adipocytes” and “white adipocytes”.

  “Hypertrophic adipocyte” is a state in which “small fat cells” accumulate fat in the cells, and in some cases, it is known that cell proliferation not seen in “small fat cells” occurs. The generation of “hypertrophic adipocytes” can cause a vicious cycle in which fat is also accumulated in newly generated adipocytes due to cell proliferation, causing significant weight gain and body shape change. Therefore, by suppressing or preventing the generation of “hypertrophic fat cells”, it is possible to prevent a significant increase in body weight and body shape change.

  Mature adipocytes include “white adipocytes” and “brown adipocytes”. “White adipocytes” are fat cells that have a function of accumulating fat, and are known to break down fat for the purpose of supplementing the energy that is deficient when falling into a state of energy deficiency such as fasting. On the other hand, “brown adipocytes” are known to oxidatively decompose fat even under normal conditions.

  It has been found that most adipocytes in adults are “white adipocytes”. In recent years, when white mitochondria cells express mitochondrial uncoupling protein 1 (UCP1) by stimulating β receptors or the like, they can exert a function similar to that of brown adipocytes, that is, a function of lipolysis. I understand. However, it is known that this phenomenon occurs in “small fat cells” but not in “hypertrophic fat cells”.

  From the above, not only preventing the increase in the number of fat cells or promoting the decrease in the number of fat cells, but also suppressing or preventing the change from “small fat cells” to “hypertrophic fat cells”, the mature fat cells in the body The abundance ratio of “small fat cells” in can be increased. If the abundance ratio of “small adipocytes” is high, it becomes possible to effectively decompose and reduce fat by activating UCP1.

  However, at present, there is no known method for suppressing or reducing the increase in mature adipocytes and suppressing or preventing the change from “small adipocytes” to “hypertrophic adipocytes”.

  For example, Patent Document 1 discloses a composition for suppressing fat accumulation in white adipocytes as a food and medicine for eliminating and preventing obesity. This composition is an internal use composition containing at least one amino acid selected from valine, leucine or isoleucine together with α-lipoic acid and coenzyme Q10. However, Patent Document 1 does not describe that adipocyte differentiation is suppressed to increase the abundance ratio of small adipocytes, and that lipolysis efficiency is improved to promote weight loss.

JP 2006-151909 A

  Normal adipocytes mature into “hypertrophic adipocytes”, which are enlarged by accumulating neutral fat in the cells by differentiation, and further enlargement and cell proliferation lead to significant weight gain. If the differentiation of adipocytes can be suppressed, weight gain can be suppressed and the number of small adipocytes, which are normal matured adipocytes, can be maintained or increased to improve the constitution that facilitates the metabolism of neutral fat. can do. By such improvement, the lipid metabolism effect by exercise can be improved, and dietary bounce caused by temporary overeating can be suppressed. Further, since the fat cells do not become enlarged, a beauty effect that a slim body shape can be maintained can be expected. Furthermore, an effect of preventing the generation of cellulite can be expected.

  Then, the objective of this invention is providing the oral composition which can suppress adipocyte differentiation, the adipocyte differentiation inhibitor, and the foodstuff containing these.

  The present inventors have intensively studied to solve the above problems, and in the presence of γ-oryzanol, accumulation of triglyceride in cells after differentiation induction of preadipocyte cell line 3T3-L1 cells is suppressed. I found out. That is, it was shown that γ-oryzanol suppresses adipocyte differentiation of cells. Moreover, it turned out that the mouse | mouth which gave (gamma) -oryzanol has the tendency for a weight to decrease compared with control. Therefore, it is speculated that γ-oryzanol suppressed the adipocyte differentiation, thereby suppressing the increase of hypertrophic adipocytes, increasing the abundance ratio of small adipocytes, improving the lipolysis efficiency, and promoting the weight loss. It was done.

  The present invention provides an oral composition for inhibiting adipocyte differentiation, containing γ-oryzanol.

  Moreover, this invention provides the oral composition in which the said (gamma) -oryzanol is contained as an extract derived from a rice bran or a rice bran in the said oral composition.

  The present invention also provides an adipocyte differentiation inhibitor containing γ-oryzanol.

  The present invention also provides an adipocyte differentiation inhibitor, wherein the γ-oryzanol is contained as a rice bran or an extract derived from rice bran.

  Moreover, this invention provides the container-packed food / beverage products containing the said adipocyte differentiation inhibitor.

  According to the present invention, as described above, since differentiation of adipocytes can be suppressed, obesity can be prevented by suppressing the increase of hypertrophic adipocytes and increasing the abundance ratio of small adipocytes. Further, by increasing the efficiency of lipolysis by activating UCP1, etc., it is possible not only to prevent obesity but also to promote weight loss, and to acquire and maintain an ideal body shape.

FIG. 2 is a diagram showing the results of macroscopic observation of cells after Oil Red O staining in Test 1, in which (a) and (b) in FIG. 1 are controls, (c) in FIG. 1 is in the presence of pioglitazone, ( d) shows the results in the presence of γ-oryzanol. FIG. 3 is a diagram showing the results of observation of cells after staining with Oil Red O in Test 1 with an optical microscope, in which FIG. 2 (a) and (b) are controls, FIG. 2 (c) is in the presence of pioglitazone, and FIG. (D) shows the results in the presence of γ-oryzanol. The graph which shows the result of having measured the fasting blood glucose level (FBG) in Test 2. FIG. The graph which shows the result of having measured the blood glucose level change after glucose administration intraperitoneally in the test 2. FIG. The graph which shows the area under a blood glucose level curve (AUC) in Test 2. FIG. The graph which shows the body weight (Body weight) at the time of dissection in the test 2. 2 is a graph showing white adipose tissue weight (WAT) during dissection in Test 2. The graph which shows the liver weight at the time of dissection in the test 2. The graph which shows the neutral fat level (TG) in the blood in the test 2. FIG. The graph which shows the free fatty acid level (NEFA) in the blood in Test 2. FIG. The graph which shows the blood glucose level (GLU) in the blood in Test 2. FIG. 3 is a graph showing the change in body weight after the start of a test meal in Test 3. 6 is a graph showing the results of measuring changes in blood glucose level after glucose administration into the abdominal cavity in Test 3. 3 is a graph showing the area under the blood glucose level curve (AUC) in Test 3. The graph which shows the body weight (Body weight) at the time of dissection in Test 3. The graph which shows the liver weight at the time of dissection in the test 3.

  The oral composition and the adipocyte differentiation inhibitor of the present invention contain γ-oryzanol.

  γ-Oryzanol is a mixture of esters of ferulic acid, mainly contained in rice bran. As γ-oryzanol, purified γ-oryzanol may be used, or rice bran or an extract derived from rice bran may be contained.

  Rice bran is produced in the rice milling process of brown rice. Red rice bran can be obtained up to about 90% of the milled rice, medium rice bran obtained up to about 85%, white rice bran obtained up to about 75%, and further refined rice can be obtained. It is classified as a special spear or white spear. Any of these may be used as the rice bran used in the present invention.

  The rice bran-derived extract may be, for example, rice bran oil or defatted rice bran. Rice bran oil is a vegetable oil extracted from rice bran, and defatted rice bran is rice bran after extracting oil from rice bran. Rice bran oil and defatted rice bran can be obtained by known methods such as a method of pressing rice bran and a method of degreasing rice bran by an organic solvent extraction method.

  The oral composition and the adipocyte differentiation inhibitor of the present invention may further contain other components of γ-oryzanol. For example, the oral composition and the adipocyte differentiation inhibitor may further contain components other than γ-oryzanol contained in rice bran. Such components include, for example, phytic acid, inositol, ferulic acid, various vitamins and various minerals.

  The oral composition and the adipocyte differentiation inhibitor of the present invention can contain known ingredients generally used in foods and pharmaceuticals and can be processed by an appropriate method in order to facilitate oral intake. .

  The oral composition and the adipocyte differentiation inhibitor of the present invention may further contain a carrier and an additive.

  As carriers and additives, excipients, binders, antioxidants, acidulants, fortifiers, fluidizers, lubricants, oligosaccharides, dietary fiber, sweeteners and flavors can be used. .

  As the excipient, for example, sugar alcohols such as maltitol, xylitol, sorbitol, erythritol, crystalline cellulose, lactose, sucrose, glucose, starch, carbonates and phosphates can be used.

  As the binder, for example, gelatin, alginic acid, xanthan gum, cellulose, hydroxypropylcellulose, methylcellulose, carrageenan, pullulan and pectin can be used.

  As the antioxidant, for example, sucrose fatty acid ester, sorbitan fatty acid ester, enzyme-treated lecithin, enzyme-decomposed lecithin, emulsifier such as saponin, ascorbic acid, tocopherol and the like can be used.

  As the sour agent, for example, lactic acid, citric acid, gluconic acid and glutamic acid can be used.

  For example, vitamins, amino acids, lactate, citrate and gluconate can be used as the fortifier.

  As the fluidizing agent, for example, silicon dioxide can be used. As the lubricant, sucrose fatty acid esters and stearates can be used.

  As the oligosaccharide, for example, lactulose, raffinose, fructooligosaccharide, isomalt-oligosaccharide, xylooligosaccharide, soybean oligosaccharide and the like can be used.

  As the dietary fiber, water-soluble dietary fiber and water-insoluble dietary fiber can be used. Examples include indigestible dextrin, cellulose, apple fiber, potato dextrose, psyllium and beet fiber.

  As the sweetener, for example, sucralose, acesulfame potassium, aspartame, thaumatin, stevia, neotame and glycyrrhizin can be used.

  For example, mint oil, eucalyptus oil, cinnamon oil, fennel oil, clove oil, orange oil, lemon oil, rose oil, fruit flavor, mint flavor, peppermint powder, dl-menthol and l-menthol it can.

  Moreover, you may mix | blend live or dead bacteria, such as lactic acid bacteria, as an additive. Further, other probiotic materials, prebiotic materials, vitamins, and plants or extracts such as herbal medicines and herbs may be added as additives.

  The oral composition and the adipocyte differentiation inhibitor of the present invention may contain conventionally known various colorants for the purpose of improving the appearance and the like. Examples of the colorant include paprika, lycopene, charcoal powder, red yeast rice powder, gardenia pigment, colored vegetable powder, algae powder such as spirulina and chlorella, and oil-solubilized pigment preparations. For the purpose of improving the texture, rice flour such as glutinous rice flour and glutinous rice flour, and starches such as tapioca starch and potato starch may be contained.

  The oral composition and the adipocyte differentiation inhibitor of the present invention further include cereals such as wheat and rice flour, beans such as soybeans and red beans, saccharides such as fruits and chickenpox, dietary fiber, water, and soybean oil and rapeseed oil. Other ingredients such as edible oil may be included. In addition, the oral composition and the adipocyte differentiation inhibitor of the present invention include other conventionally added foods such as sweeteners, antioxidants, vitamins, minerals, fragrances, and pigments, which are conventionally known food additives. Ingredients may be included.

  The oral composition and the adipocyte differentiation inhibitor of the present invention can be used for foods and drinks, pharmaceuticals and quasi drugs. When it is a food or drink, it can be, for example, a general food, a food for specified health use, a nutritional supplement, a functional food, a food for the elderly, a supplement, a confectionery, or the like. In the case of a pharmaceutical product or quasi-drug, either an internal medicine or an external medicine may be used, but if it is an internal medicine, a high effect can be obtained.

  Examples of the oral composition and the adipocyte differentiation inhibitor of the present invention include liquids, tablets, granules, fine granules, powders, tablets, capsules, liquids, pastes, gels, and other generally foods and beverages and pharmaceuticals. Can be ingested as a form.

  The present invention also includes foods and drinks containing the adipocyte differentiation inhibitor described above. Examples of foods and drinks include general foods, special-purpose foods such as foods for specified health use and foods for the sick, functional foods such as dietary supplements, diet foods and beauty foods, foods for the elderly, supplements, beverages and confectionery. Can be.

  The food / beverage products of this invention may be provided as a container-packed food / beverage product. The container-packed food / beverage product of the present invention is a food / beverage product provided in a state where the food / beverage product containing the above-described adipocyte differentiation inhibitor is filled in a container and sealed. That is, the container-packed food / beverage of this invention is a container-packed food / beverage containing γ-oryzanol for suppressing adipocyte differentiation. The food and drink may be filled in the container after the sterilization treatment.

  The container-packed food / beverage products of this invention may be ingested after being concentrated and diluted, or may be ingested without dilution. As a container, the container generally used for food-drinks can be used, for example, a retort pouch, a paper pack, a PET bottle, a metal can, a glass bottle, etc. can be used.

  The content of γ-oryzanol contained in the oral composition, the adipocyte differentiation inhibitor and the container-packed food and drink of the present invention is not particularly limited, but from the viewpoint of effectively inhibiting adipocyte differentiation, 0.1 mg It may be ˜500 mg / 100 g, such as 1 mg to 100 mg / 100 g and 5 mg to 50 mg / 100 g.

  As shown in the following examples, γ-oryzanol contained in the present invention improves a constitution that facilitates lipolysis by suppressing adipocyte differentiation and maintaining or increasing the amount of small adipocytes, and diet control In addition to improving the diet effect obtained by exercise, there is a possibility of improving fat resolution in normal times. Therefore, the present invention can be optimally used as diet foods, beauty foods, foods for exercise therapy, obesity treatment foods, and the like. The present invention can be a food or drink with an indication that it is suitable for diet, beauty or obesity improvement. It also has the aspect of preventing the generation of hypertrophic adipocytes, so it can contribute to the prevention and improvement of obesity, diabetes and various diseases related to them, obesity, metabolic syndrome, diabetes, arteriosclerosis, impaired glucose tolerance, hypertension It can also be used in oral compositions, pharmaceuticals, foods and drinks for the prevention and improvement of hyperlipidemia, hypertriglyceremia, hypercholesterolemia and liver diseases. In addition, the present invention can be used for oral compositions, pharmaceuticals, foods and drinks for the prevention and improvement of diabetic complications such as periodontal disease (gingivitis, periodontitis). Moreover, this invention can also be made into the food / beverage products which attached | subjected the indication that it was suitable for prevention or improvement of the disease mentioned above.

  The test results for γ-oryzanol are shown below.

[Test 1]
In vitro tests were performed using preadipocytes 3T3-L1 cells. 3T3-L1 cells are isolated from mouse fibroblasts as a strain that accumulates fat. Since the cells themselves are immortalized, they can proliferate in large quantities as fibroblasts before induction of differentiation. . Further, 3T3-L1 cells can be induced to differentiate more than 95% in adipocytes by insulin, dexamethasone and 3-isobutyl-1-methylxanthine (IBMX).

(Medium preparation)
As the subculture medium, subculture medium A (DMEM (4.5 g.mL Glu) (Sigma, glucose, D5769), 10% BS (Gibco, 16170, lot # 990250) and 1% antibiotic (Gibco, Antibiotic-Antimycotic, 15240-062)), and passage medium B (DMEM (4.5 g.mL Glu), 10% FBS (Biowest, S1560, lot # SO5094S1560) and 1% antibiotics) were used. BS and FBS were inactivated (56 ° C., 30 minutes).

  For differentiation induction medium, subculture medium B was supplemented with 10 μg / mL insulin solution (Wako, 093-06351, lot # DOG7017), 0.25 μM Dexamethasone (DEX) (Sigma, D4902) and 0.11 mg / mL IBMX (3-isobutyl 1-methylxanthine) (Sigma, 15879) was used. As the differentiation promoting medium, a medium obtained by adding 5 μg / mL insulin solution to subculture medium B was used. Differentiation induction medium and differentiation promotion medium were prepared at the time of use.

(Sample preparation method)
[Pioglitazone]
The thiazolidine derivative pioglitazone, which is thought to promote adiponectin secretion and promote adipocyte differentiation, was used as a control. Pioglitazone hydrochloride (Wako, 1ot # LAN0167, WEL4297) was dissolved in DMSO and prepared in a medium to a final concentration of 10 μM.

[Γ-oryzanol]
A γ-oryzanol solution prepared by dissolving γ-oryzanol (TCI, O0172) in DMSO and adjusting the concentration to 5 mM was used. In the experiment, it was diluted with a medium so that the final concentration was 5 μM.

(Cell culture and sample addition method)
3T3-L1 cells (Dainippon Sumitomo Pharma Co., Ltd., Embryo mouse) are grown in the necessary amount in the subculture medium A, and 1.5 × 10 ^{4 in} a 12-well collagen-coated culture plate (Sumitomo Bakelite, Sumilon Celtite C-1). Seed 1 mL of cell suspension (2 mL for 6-well plate) to a concentration of ce1l / well (3.75 x 10 ⁴ ce11 / well for 6-well plate), 37 ° C, 5% Incubated for 2 days under CO ₂ . Thereafter, the medium was replaced with the subculture medium B. After confluence, the culture was continued in the subculture medium B for 1-2 days, and the culture medium was replaced with a differentiation-inducing medium (day 0). Within 48 hours after differentiation induction with the differentiation induction medium, the medium was replaced with a differentiation promotion medium (day 2). Each sample was continuously added from the time of differentiation induction medium exchange (day 0) to day 7-8.

(Oil Red staining method of fat cells)
[Reagent preparation]
Cold 10% formalin / PBS (pH 7.4) was prepared by adding 10% (v / v) formalin to PBS and adjusting to pH 7.4, and stored at 4 ° C. In this test, 10% neutral buffered formalin solution (Wake, 060-03845) was used.

  A 0.5% Oil Red O / isopropanol solution was used as the staining solution. Oil Red O (Wake, 154-02072) was dissolved in isopropanol (Sigma) by shaking well with a stirrer to prepare a saturated solution. Left at least 5 days after preparation. Immediately before use, a 0.5% Oil Red O / isopropanol solution and distilled water were mixed at a ratio of 3: 2 and left at room temperature for 10 minutes (preparation at the time of use).

[Dyeing method]
Using the above culture method, 3T3-L1 cells in a 6-well plate cultured until day 7-8 were used. With the medium contained, cold 10% formalin / PBS was added at 1 ml / well and left at room temperature for 20 minutes. The medium was removed by decantation, and 1.5 ml / well of cold 10% formalin / PBS was newly added and left at room temperature for 1 hour. The formalin solution was removed by decantation, washed 2-3 times with distilled water (1 ml / well), and the remaining distilled water was completely removed with a Pipetman. After washing once with 60% isopropanol (1 ml / well), 1 ml / well of the passed staining solution was added and left at room temperature for 1 hour. After staining, the cells were washed once with 60% isopropanol (1 ml / well) and washed 2-3 times with distilled water (1 ml / well). Microscopic observation was carried out in a water-filled state, and a photograph was taken. Also, after thoroughly air-drying, the whole picture was taken with a scanner.

(Results of Oil Red O staining)
In the presence of each sample, oil droplets of 3T3-L1 cells on day 7 to 8 on which differentiation was promoted by the above culture method were stained red with Oil Red O staining. FIG. 1 is a diagram showing the result of observation of cells after Oil Red O staining with the naked eye. FIG. 2 is a diagram showing the results of observation of cells after Oil Red O staining with an optical microscope. FIGS. 1 (a) and (b) and FIG. 2 (a) and (b) show the results of the control with no sample added. 1 (c) and FIG. 2 (c) show the results in the presence of pioglitazone, and FIG. 1 (d) and FIG. 2 (d) show the results in the presence of γ-oryzanol.

  As shown in FIGS. 1 and 2, accumulation of triglyceride was observed in the cells of control and pioglitazone, and it was confirmed that differentiation into adipocytes was strongly promoted. On the other hand, in the presence of γ-oryzanol, the portion stained in red was clearly small, and it was confirmed that triglyceride was not accumulated in the cells. That is, it was suggested that γ-oryzanol suppresses differentiation into adipocytes.

[Tests 2 and 3]
Next, an in vivo test was performed using mice.

(Test meal)
A high fat diet (HFD) having the following composition and a feed containing γ-oryzanol (γ-oryzanol) were used for the test meal (produced by Oriental Yeast Co., Ltd.). As γ-oryzanol, γ-oryzanol (Wako, 152-01272) was used. Each feed is solid, usually dried (90 ° C., 90 minutes), and irradiated with γ rays (30 kGy). Moreover, AIN-93M adjusted meal (made by Oriental Yeast Co., Ltd.) was used as a normal meal (CTL).

(Raising conditions)
They were raised on a floor (ALPHA-driTM) and given filtered water (free intake) as drinking water. The breeding conditions were a temperature of 20 to 25 ° C., a humidity of 45 to 70%, and a daily lighting time of 12 hours. After preliminary breeding with a normal diet (CE-2 solid), the body weight was measured, and after grouping so that there was no significant difference in the average value of the weight of each group, the test diet was started.

(IpGTT method)
After fasting overnight (15 hours), the tail of the animal was punctured and the blood glucose level was measured using a simple blood glucose level measuring device (fasting blood glucose level). After measuring the fasting blood glucose level, 1.5 g / kg BW (40% w / v solution) was administered intraperitoneally in Test 2 and 2 g / kg BW glucose was administered intraperitoneally in Test 3. Every predetermined time after intraperitoneal administration of glucose, the tail was punctured in the same manner as fasting blood glucose measurement, and the blood glucose level was measured using a simple blood glucose measurement device.

(Anatomy method)
After fasting, the animals were opened under anesthesia with isoflurane (furan, 1-chloro-2,2,2-trifluoroethyldifluoromethyl ether), blood was collected from the inferior vena cava, and blood was killed. An injection needle through which heparin sodium was passed was used. The collected blood was stored after being brought to a plasma state by centrifugation. After death from blood loss, the liver and white adipose tissue were removed and used for analysis. Each extracted tissue was washed with PBS (−) to remove excess water, frozen with liquid nitrogen, and stored at −80 ° C. until used for analysis.

(Method for measuring liver lipids)
A set of tissue destruction devices (Microtech Nithion) was sufficiently cooled with liquid nitrogen, and the liver was shattered using them. Place the crushed liver into a glass conical tube containing 0.5M acetic acid (Sigma), methanol (Sigma) and chloroform (Sigma) (1: 2.5: 1.25), homogenize for 2 minutes, vortex for 20 seconds, and then 10 minutes Left at room temperature. Thereafter, chloroform was added and vortexed for 20 seconds, 0.5M acetic acid was added and vortexed for 1 minute. Centrifugation was performed at 1,500 × g for 10 minutes (4 ° C.), and the lower layer was transferred to another container using a Pasteur pipette. Chloroform was added to the remaining upper layer again, vortexed for 1 minute, centrifuged at 1,500 × g for 10 minutes (4 ° C.), and re-extracted. The collected lower layer was dried in a fume hood and dissolved by vigorously stirring with a mixed solution of isopropyl alcohol (Sigma): TritonX100 (Sigma) = 9: 1. About the obtained sample solution, the lipid in liver was measured using cholesterol E-test Wako (Wake, 439-17501) and triglyceride E-test Wako (Wake, 432-40201).

(Test 2)
After administration of body weight and glucose in diabetic mice KK-Ay / TaJcld (obtained from Claire Japan), group fed with high fat diet (HFD) and group fed γ-oryzanol-containing feed Changes in blood glucose level, tissue weight and blood index were measured. Mice were raised individually. Water and food were ad libitum.

  In the feeding method, the amount of food intake for each day was measured, and the average daily food intake was calculated.

[Weight change]
Body weight was measured at the same time every week. The change in body weight after the start of the test meal was not significantly different in the γ-oryzanol group compared to the high fat diet (HFD) group (not shown).

[IpGTT]
FIG. 3 shows the results of measuring fasting blood glucose level (FBG) by ipGTT for each group. In addition, FIG. 4 shows the result of measuring the change in blood glucose level after administration of glucose intraperitoneally by ipGTT. In addition, the results of calculating the area under the blood glucose level curve (AUC) for each group are shown in FIG.

  The fasting blood glucose level (FBG) of the γ-oryzanol group was lower than that of the HFD group (FIG. 3). In addition, after administering glucose intraperitoneally, especially after 60 minutes, the blood glucose level of the γ-oryzanol group was significantly lower than that of the HFD group (FIG. 4). The area under the blood glucose curve (AUC) of the γ-oryzanol group was also significantly lower than that of the HFD group (FIG. 5).

[Body weight and tissue weight]
Each group was raised on each test meal for 25 days or 26 days, and then dissection was performed, the tissue was collected, body weight (Body weight), white adipose tissue (sub-skew circumference fat) weight (WAT), and Liver weight (LIVER) was measured. The results are shown in FIGS. The γ-oryzanol group had the same body weight as the HFD group, but both the white adipose tissue weight and the liver weight showed lower values.

[Blood index]
Blood samples collected at the time of dissection were made into plasma by centrifugation, and then blood neutral fat level (TG), free fatty acid level (NEFA), blood glucose level (GLU) and insulin level (INS) were measured. The results are shown in FIGS.

  As a result, the triglyceride level (TG), free fatty acid level (NEFA), and blood glucose level (GLU) decreased in the γ-oryzanol group as compared with the HDF group.

(Test 3)
Using normal mouse C57BL6J (obtained from Charles River Japan), change in body weight in group fed with normal diet (CTL), group fed with high fat diet (HFD), and group fed with γ-oryzanol Changes in blood glucose level and tissue weight after glucose administration were measured. Mice were housed in groups of 4 / cage. The pre-feeding period and the food after the start of the test meal were freely consumed.

[Weight change]
Body weight was measured at the same time every week. The change in body weight after the start of the test meal is shown in FIG. Compared to the HFD group, the body weight of the CTL group was significantly reduced. In addition, the body weight of the γ-oryzanol group was always lower than that of the HFD group. In addition, there was no difference in food intake in any group (not shown).

[IpGTT]
FIG. 13 shows the results of measuring blood glucose level changes after ip administration into the peritoneal cavity by ipGTT for each group. FIG. 15 shows the results of calculating the area under the blood glucose level curve (AUC) for each group. As shown in FIG. 13 and FIG. 14, in the CTL group, the glucose level was significantly lowered and the AUC was significantly lower at all times after administration of glucose into the abdominal cavity as compared with the HFD group. In the γ-oryzanol group, the blood glucose level was significantly reduced 30 minutes and 60 minutes after glucose administration, and AUC was also significantly lower than in the HFD group.

[Body weight and tissue weight]
Each group was raised on each test diet for 99 days or 100 days, and then dissection was performed. Tissues were collected and body weight and liver weight (LIVER) were measured. The results are shown in FIGS. 15 and 16, respectively. The HFD group was significantly increased in all items compared to the CTL group. On the other hand, in the γ-oryzanol group, which was a diet group in which γ-oryzanol was added to the HFD group, both body weight and liver weight were lower than in the HFD group.

[Discussion]
From the results of Test 1, it is considered that in the presence of γ-oryzanol, accumulation of triglyceride in 3T3-L1 was suppressed, and thus differentiation was suppressed. In Test 3, the C57BL6J mice fed with γ-oryzanol always showed a low body weight compared to the high fat diet group, and therefore, γ-oryzanol inhibited adipocyte differentiation. It can be assumed that the enlargement was suppressed. That is, γ-oryzanol not only suppresses the increase of hypertrophic adipocytes by suppressing adipocyte differentiation but also suppresses the increase in body weight, but also increases the abundance ratio of small adipocytes having a lipolytic function. It was suggested that it has the effect of improving efficiency and reducing body weight.

  In Tests 2 and 3, in γ-oryzanol group, blood glucose level after intraperitoneal glucose administration was significantly reduced compared to HFD group, so that γ-oryzanol suppresses adipocyte differentiation. This suggested that the decrease in adiponectin secretion due to the decrease in small adipocytes was suppressed, and as a result, insulin resistance was improved. That is, it was suggested that γ-oryzanol has an action of improving insulin resistance by suppressing adipocyte differentiation.

  The present invention can be suitably used for diet foods, beauty foods, foods for exercise therapy, obesity treatment foods, etc., and also obesity, metabolic syndrome, diabetes, arteriosclerosis, impaired glucose tolerance, hypertension, high fat It can also be used in oral compositions, pharmaceuticals, foods and drinks, etc. for the prevention and improvement of blood glucose, hypertriglyceridemia, hypercholesterolemia, liver disease and periodontal disease.

Claims (5)

  An oral composition for inhibiting adipocyte differentiation, comprising γ-oryzanol.   The oral composition for suppressing adipocyte differentiation according to claim 1, wherein the γ-oryzanol is contained as rice bran or an extract derived from rice bran.   An adipocyte differentiation inhibitor containing γ-oryzanol.   The adipocyte differentiation inhibitor according to claim 3, wherein the γ-oryzanol is contained as rice bran or an extract derived from rice bran. Container-packed food-drinks containing the adipocyte differentiation inhibitor of Claim 3 or 4.