JP5731738B2 - Adipocyte differentiation inhibitor - Google Patents

Description

  The present invention relates to an adipocyte differentiation inhibitor.

  Obesity is a problem as a risk factor for lifestyle-related diseases such as diabetes, dyslipidemia, and hypertension. As an anti-obesity agent, for example, one containing a hydrolyzate of wheat protein is known (see Patent Document 1). Moreover, what contains (alpha)-or (gamma) -tocotrienol or its in-vivo metabolite is known (refer patent document 2).

JP 2007-106683 A JP 2007-277187 A

  By the way, obesity is formed by the differentiation of preadipocytes into adipocytes (mature adipocytes) and their number and size increase. To suppress obesity, adipocytes of preadipocytes are used. It is effective to suppress differentiation. Although some adipocyte differentiation inhibitors are known (see, for example, Patent Document 2), it is the actual situation that there are still no sufficient options to meet the diverse demands of consumers.

  Then, this invention makes it a subject to provide a novel adipocyte differentiation inhibitor.

  The present invention provides an adipocyte differentiation inhibitor containing a water extract of hop tissue as an active ingredient. In the present invention, the “water extract” refers to an extract with water of 0 to 50 ° C. (excluding 0 ° C.).

  The adipocyte differentiation inhibitor of the present invention suppresses the expression of PPAR (peroxisome proliferator-activated receptor) γ and suppresses adipocyte differentiation (differentiation of preadipocytes into adipocytes) through this. Then, through suppression of adipocyte differentiation, obesity and various symptoms or diseases caused by it (for example, diabetes, dyslipidemia, hypertension) can be prevented or improved (treated or reduced). PPARγ is known to promote the differentiation of preadipocytes into adipocytes.

  Since the adipocyte differentiation inhibitor of the present invention suppresses the expression of PPARγ, it can also be used as a PPARγ expression inhibitor. That is, the present invention also provides a PPARγ expression inhibitor containing a water extract of hop tissue as an active ingredient.

  In the present invention, the hop tissue for obtaining the water extract is preferably a stalk, bud (especially bud) or leaf, and particularly preferably bud.

  Hops are plants that have been used mainly for beer brewing since ancient times, and have been used for various purposes other than brewing, and safety for living bodies has been established. Therefore, the adipocyte differentiation inhibitor and PPARγ expression inhibitor of the present invention are highly safe for living bodies and can be ingested continuously for a long period of time, such as pharmaceuticals, foods and drinks, food and drink additives, feeds, feed additives, etc. It is suitable for use as a component of That is, the present invention also provides a pharmaceutical, a food, a food, a food additive, a feed, a feed additive and the like containing the adipocyte differentiation inhibitor or the PPARγ expression inhibitor.

  Since hops contain bitter components, it has been difficult to use them for food and drink other than effervescent alcoholic beverages (for example, beer). However, the water extract of a hop structure | tissue has low content of a hop bitterness component, and can be easily mixed with food-drinks. Also in this respect, the adipocyte differentiation inhibitor and the PPARγ expression inhibitor of the present invention are suitable for use as components of food and drink.

  According to the present invention, a novel adipocyte differentiation inhibitor and PPARγ expression inhibitor are provided. Moreover, the pharmaceutical, food / beverage products, food / beverage product additive, feed, feed additive, etc. containing such an adipocyte differentiation inhibitor or a PPAR (gamma) expression inhibitor are provided.

It is a graph which shows the mesentery fat weight of the mouse | mouth which administered the water extract of the hop tissue. It is a graph which shows the abdominal wall fat weight of the mouse | mouth which administered the water extract of the hop tissue. It is a graph which shows the weight of fat around the testicle of the mouse | mouth which administered the water extract of the hop tissue. It is a graph which shows the intraperitoneal fat weight of the mouse | mouth which administered the water extract of the hop tissue. It is a graph which shows the mesentery fat cell size of the mouse | mouth which administered the water extract of the hop tissue. It is a graph which shows the abdominal wall fat cell size of the mouse | mouth which administered the water extract of the hop tissue. It is a graph which shows the adipocyte periphery fat cell size of the mouse | mouth which administered the water extract of the hop tissue. It is a graph which shows the expression level of PPAR (gamma) mRNA in the liver of the mouse | mouth which administered the water extract of the hop tissue.

  Hereinafter, preferred embodiments of the present invention will be described.

  The adipocyte differentiation inhibitor and PPARγ expression inhibitor of the present invention contain a water extract of hop tissue as an active ingredient.

  In the present invention, the “hop organization” means any or a part of a hop organization. As a hop structure | tissue used for water extraction, a stem, a flower (especially bud) or a leaf is preferable, and a cocoon is especially preferable. Hop lees can be obtained, for example, as a by-product during beer brewing. The use of firewood also contributes to effective use of firewood.

  The hop varieties for obtaining the water extract are not particularly limited. For example, Czech Saats, German Haratau Magnum, German Haratau Tradition, German Perle, German Hertzbrucker, American Nugget species, New Zealand Pacific Haratau species, or Japanese Furano No. 18 can be used. Further, only one kind of hop may be used, or two or more kinds of hops may be used in combination.

  The hop tissue subjected to water extraction may be subjected to treatments such as drying, freezing, processing, pulverization, and selection. For example, hop spikelets may be dried, frozen, and pulverized to remove pulverized material of a certain size or less.

  The hop tissue is preferably dried at a temperature of 55 ° C. or less until the water content becomes 10% by mass or less. The method for freezing the hop tissue is not particularly limited, but the freezing temperature is preferably −10 ° C. or lower, and particularly preferably −35 ° C. or lower. The hop structure can be pulverized using, for example, a pulverizer such as a pin mill, a hammer mill, or a ball mill. In order to select the hop tissue by size, for example, the hop tissue may be passed through a sieve having a certain size (for example, 0.1 mm, 0.3 mm, 0.5 mm).

  As the hop tissue, for example, a hop residue obtained by removing an extract of hop spikelets with an organic solvent or a supercritical fluid from the spikelets can be used. As an organic solvent, alcohol and hexane are mentioned, for example, A C1-C4 lower alcohol is preferable and ethanol is especially preferable. Examples of the supercritical fluid include carbon dioxide, water, methane, ethane, ethylene, propane, pentane, methanol, and ethanol, and carbon dioxide is preferable.

  In the present invention, the “water extract” means an extract with water of 0 to 50 ° C. (excluding 0 ° C.). The temperature of water becomes like this. Preferably it is 1-40 degreeC, More preferably, it is 5-30 degreeC.

  The water extraction of the hop tissue can be performed according to a conventional method. For example, a hop structure and water are put in a container and left to stand for a predetermined time with appropriate stirring. The liquid obtained by standing can be used as a water extract as it is. Further, for example, a supernatant obtained by centrifuging such a liquid can be used as a water extract. Moreover, such a liquid or supernatant can be concentrated and dried to remove water, and this can be used as a water extract. Water extraction may be performed by adding a small amount (10% by mass or less) of alcohol (preferably ethanol) to water in order to increase extraction efficiency and shorten extraction time.

  The adipocyte differentiation inhibitor and PPARγ expression inhibitor of the present invention may be in any form such as solid (for example, powder obtained by freeze-drying), liquid (water-soluble or fat-soluble solution or suspension), paste, and the like. In addition, any dosage form such as powders, granules, tablets, capsules, solutions, suspensions, emulsions, ointments, plasters and the like may be used. Further, the adipocyte differentiation inhibitor and PPARγ expression inhibitor of the present invention may be composed of an aqueous extract of hop tissue.

  The above-mentioned various preparations include a water extract of hop tissue and pharmaceutically acceptable additives (excipients, binders, lubricants, disintegrants, emulsifiers, surfactants, bases, solubilizers, And a suspending agent, etc.).

  For example, the excipient includes lactose, sucrose, starch, dextrin and the like. Examples of the binder include polyvinyl alcohol, gum arabic, tragacanth, gelatin, hydroxypropylmethylcellulose, hydroxypropylcellulose, sodium carboxymethylcellulose, polyvinylpyrrolidone and the like. Examples of the lubricant include magnesium stearate, calcium stearate, talc and the like. Examples of the disintegrant include crystalline cellulose, agar, gelatin, calcium carbonate, sodium bicarbonate, dextrin and the like. Examples of the emulsifier or surfactant include Tween 60, Tween 80, Span 80, and glyceryl monostearate. Examples of the base include cetostearyl alcohol, lanolin, polyethylene glycol, rice bran oil, fish oil (DHA, EPA, etc.), olive oil and the like. Examples of the solubilizer include polyethylene glycol, propylene glycol, sodium carbonate, sodium citrate, Tween 80 and the like. Examples of the suspending agent include polyvinyl alcohol, polyvinyl pyrrolidone, methyl cellulose, hydroxymethyl cellulose, sodium alginate and the like in addition to the above-described surfactant.

  The adipocyte differentiation inhibitor and PPARγ expression inhibitor of the present invention can be used by adding to beverages, foods, feeds and the like. Examples of drinks that can be added include water, soft drinks, fruit juice drinks, milk drinks, and alcoholic drinks. Examples of foods that can be added include grain meals such as rice and barley rice, and powdered meals such as wheat flour. In particular, foods such as noodles, breads and sweets made of wheat flour are suitable for addition. Furthermore, processed foods made from wheat (for example, miso and soy sauce) are also subject to addition. The adipocyte differentiation inhibitor and PPARγ expression inhibitor of the present invention can also be used as components for foods for specific health use, foods for special uses, food supplements, health foods, functional foods, foods for the sick, and the like. The content ratio of the adipocyte differentiation inhibitor or PPARγ expression inhibitor with respect to the total mass of beverages, foods and the like is preferably 5% by mass or more, more preferably 10% by mass or more, further preferably 20% by mass or more, and particularly preferably 30%. It is at least mass%.

  The beverage, food, feed and the like may further contain additives usually used in the field. Examples of such additives include bitters, flavorings, apple fiber, soybean fiber, meat extract, black vinegar extract, gelatin, corn starch, honey, animal and vegetable oils and fats; proteins such as gluten; beans such as soybeans and peas; glucose Monosaccharides such as fructose; disaccharides such as sucrose; polysaccharides such as dextrose and starch; sugar alcohols such as erythritol, xylitol, sorbitol and mannitol; vitamins such as vitamin C; minerals such as zinc, copper and magnesium Functional materials such as CoQ10, α-lipoic acid, carnitine, capsaicin; These additives can be used alone or in combination of two or more.

  The adipocyte differentiation inhibitor and PPARγ expression inhibitor of the present invention may be administered to humans or non-human mammals. The dosage and administration method can be appropriately determined according to the condition, age, etc. of the individual to be administered. Suitable administration methods include, for example, oral administration.

  Hereinafter, based on an Example, this invention is demonstrated more concretely. However, the following examples do not limit the present invention.

  Tests for confirming the adipocyte differentiation inhibitory action and PPARγ expression inhibitory action of the hop tissue water extract were performed as follows.

(Mouse grouping)
As a mouse, a 4-week-old male C57BL / 6J mouse (Nippon Charles River) was used. After one week of acclimatization and breeding, select 35 mice with good general condition and positive control group, water extract 0.5% group, water extract 2. It was divided into 4 groups of 0% group and negative control group (positive control group, water extract 0.5% group, water extract 2.0% group 10 each, negative control group 5). Throughout the acclimatization breeding period and the subsequent test period, the mice had a temperature of 22 ± 3 ° C., a relative humidity of 55 ± 20%, a ventilation rate of 12 times / hour, and a light / dark time of 12 hours (light period: 8:00 to 20:00). Breeding under conditions.

(Preparation of water extract of hop tissue)
A commercially available hop water extract (CZ-01, Sapporo Agency) was used as the water extract of the hop tissue. CZ-01 is an aqueous extract of hop camellia (Czech zats species).

(Feed preparation)
The feed to be administered to the mice of each group during the test period was prepared based on the powder feed AIN93G so as to obtain the composition shown in Table 1. In the table, the unit of each component amount is g / kg feed.

(Food administration)
After the acclimation breeding described above, each group of mice was allowed to freely ingest predetermined feed and water for 4 weeks. During the acclimation breeding period, all mice were allowed to freely ingest a normal diet (the composition was the same as the feed administered to the negative control group mice during the test period).

(Measurement of fat weight, adipocyte size, PPARγ expression level)
After completion of the 4-week test period, each group of mice was subjected to cardiac blood sampling and dissection under ether anesthesia, mesenteric fat weight (g / 100 g body weight), retroabdominal wall fat weight (g / 100 g body weight), accessory testicle Peripheral fat weight (g / 100 g body weight), mesenteric adipocyte size (major axis) (μm), retroabdominal wall adipocyte size (major axis) (μm), and epididymal fat cell size (major axis) (μm) were measured. .

  Moreover, the liver was extracted from the mouse and the expression level of PPARγ was measured. Specifically, first, total RNA was extracted from the liver using Trizol (Invitrogen) and purified with RNeasy Mini Kit (Qiagen). Then, cDNA was prepared from RNA using QuantitTect Reverse Transcription Kit (Qiagen), and PPARγ mRNA expression level was measured by real-time PCR using SYBR Green.

  The results are shown in Tables 2 to 5 and FIGS. FIG. 1 is a graph showing mesenteric fat weight of each group of mice. FIG. 2 is a graph showing the weight of fat in the rear abdominal wall of each group of mice. FIG. 3 is a graph showing the fat weight around the epididymis of each group of mice. FIG. 4 is a graph showing the intraperitoneal fat weight of each group of mice. FIG. 5 is a graph showing the mesenteric adipocyte size of each group of mice. FIG. 6 is a graph showing the abdominal wall fat cell size of each group of mice. FIG. 7 is a graph showing the size of adipocytes around the epididymis of each group of mice. FIG. 8 is a graph showing the expression level of PPARγ mRNA in the liver of each group of mice.

  In addition, data are shown by the average +/- standard error except the data of abdominal fat weight (Table 3, FIG. 4). In addition, the data of intraperitoneal fat weight (Table 3, FIG. 4) are mesenteric fat weight (Table 2, FIG. 1), retroabdominal wall fat weight (Table 2, FIG. 2), and epididymal fat weight (Table 2). FIG. 3) is a sum of the data (average). In Table 5 and FIG. 8, the PPARγ mRNA expression level is shown as a ratio to the simultaneously measured GAPDH (glyceraldehyde 3-phosphate dehydrogenase) mRNA expression level.

  As apparent from Tables 2-5 and FIGS. 1-8, mesenteric fat weight, retroabdominal wall fat weight, epididymal fat weight, intraperitoneal fat weight, mesenteric fat cell size, retroabdominal wall fat cell size, Both the size of adipocytes and the amount of PPARγ mRNA expression were higher in the positive control group than in the negative control group. Moreover, all show a low value in the water extract 0.5% group and the water extract 2.0% group, particularly in the water extract 2.0% group, compared with the positive control group. showed that.

  According to the above examples, the water extract of hop tissue can suppress adipocyte differentiation through suppression of PPARγ expression, and is useful as a component of an adipocyte differentiation inhibitor and a PPARγ expression inhibitor. confirmed.

  The adipocyte differentiation inhibitor and PPARγ expression inhibitor of the present invention are useful for the prevention and improvement of obesity.

Claims (3)

  A PPARγ expression inhibitor containing a water extract of hop tissue as an active ingredient.   The PPARγ expression-suppressing agent according to claim 1, wherein the tissue is a stem, a spike or a leaf.   The PPARγ expression inhibitor according to claim 1, wherein the tissue is sputum.

Images