JP2009256309A - Fat-metabolism improving gene manifestation accelerant and diabetes prevention-related gene manifestation accelerant - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a new fat-metabolism improving gene manifestation accelerant, such as aquaporin 7, PPARγ, adiponectin, GLUT4 and insulin receptor, accelerating manifestation of genes having functions preventing from life style-related diseases. <P>SOLUTION: The fat-metabolism improving gene manifestation accelerant or the like includes an extract from Rosaceae Fragaria L. as an effective component. Also, it is preferable that the extract contains tiliroside. Furthermore, it is preferable that the extract uses seeds as the portion of the Rosaceae Fragaria L. Furthermore, the agent can be widely utilized as food and drink, medicines, external use agents for skin, and the like. <P>COPYRIGHT: (C)2010,JPO&INPIT

Description

  The present invention relates to a fat metabolism improving gene expression promoting agent and a diabetes related gene expression promoting agent comprising a novel component as an active ingredient. The present invention is widely used for pharmaceuticals, foods and drinks, external preparations for skin, and the like.

  Modern people are more likely to have obesity and hyperlipidemia due to the Western type of diet, high calorie and high fat diet. Obesity and hyperlipidemia are known not only as arteriosclerotic diseases such as myocardial infarction and angina, but also as risk factors for lifestyle-related diseases such as diabetes and hypertension.

In fact, these lifestyle-related diseases, together with cancer, occupy the top mortality rate in recent years and are a serious problem. Since obesity and hyperlipidemia often significantly promote fat synthesis, improving this lipid metabolism to a normal level is an important issue for the prevention and treatment of lifestyle-related diseases. Therefore, in order to improve lipid metabolism, adiponectin, PPAR (Peroxisome Proliferator Activated
Receptors: Peroxisome proliferator-activated receptors), glucose transporters, and insulin receptors that promote the expression of genes have been developed.

  Adiponectin is a hormone secreted from adipose tissue composed of 244 amino acids, and activates AMP kinase (AMP-activated protein kinase: AMPK) in skeletal muscle and liver, thereby burning fat and It is known to promote sugar uptake. Adiponectin is secreted in a large amount in small adipocytes, but it is known that the amount of secretion decreases when adipocytes are enlarged.

  Adiponectin is also known as a good adipocytokine that suppresses arteriosclerosis. In addition to the above-mentioned good adipocytokines, adipocytokines include bad adipocytokines that promote arteriosclerosis such as PAI-1 and TNF-α. Under normal conditions, the amount of secretion of these good and bad adipocytokines is balanced. However, when fat cells are enlarged due to obesity or the like, the amount of good adipocytokines secreted decreases, while the amount of bad adipocytokines is excessively secreted. As a result, the balance between the two is lost, and it is considered that it causes lifestyle-related diseases such as type 2 diabetes and arteriosclerosis.

  Thus, adiponectin is involved in obesity and lifestyle-related diseases associated with obesity, and activating this adiponectin is considered to be effective in preventing or treating lifestyle-related diseases. Furthermore, adiponectin is also known to have a liver fibrosis inhibiting effect, a normal hepatocyte proliferation promoting effect (Patent Document 1), an anti-inflammatory effect (Patent Document 2), and the like.

In addition, PPAR (Peroxisome Proliferator Activated
Receptor (peroxisome proliferator-activated receptor) is a nuclear receptor that was identified in 1990 as a protein that mediates the action of increasing peroxisomes, which are intracellular organelles involved in lipolysis. Peroxisome Proliferator Activated in the sense of a receptor that is activated by an agent
It was named Receptorα (peroxisome proliferator activated receptor: PPARα). Subsequently, β / δ type and γ type were identified as isoform genes structurally similar to α type, and it is known that it consists of a total of three subtypes. Since there are two promoters in human and mouse γ-type genes, there are two types of proteins, PPARγ1 and PPARγ2, which differ in N-terminus due to differences in splicing. Each subtype of PPAR is activated in a ligand-dependent manner, forming a heterodimer with RXR (Retinoid X Receptor), which uses 9-cis retinoic acid as a ligand, and responds to the PPAR response in the promoter region (transcriptional control region). Array (PPAR
It regulates the expression of various genes with responsive element (PPRE). In recent years, it has become clear that PPAR is involved in numerous physiological and pathological phenomena. In particular, the function of PPARα is thought to be related to the maintenance of energy metabolism and homeostasis in a wide range, including fatty acid synthesis, transport and secretion, ATP production in fat-consuming organs, and regulation of the cell cycle. Particularly important enzymes for fatty acid metabolism such as β-oxidation (Acyl-CoA oxidase, HMG-CoA synthase, Acyl-CoA synthase, Medium chain)
It has been revealed that gene expression of acyl dehydrogenase, fatty acid binding protein, lipoprotein lipase, etc.) strongly depends on the activation of PPAR. In other words, it has become clear that a PPAR activator has an action of activating lipid metabolism in a living body. Activation of biological lipid metabolism is a useful action that leads to improvement of hyperlipidemia and anti-obesity. In addition, PPARγ, particularly PPARγ2, is expressed with relatively strong specificity in adipocytes, and has been shown to play a central role in adipocyte differentiation. (Cell: 31 (6), 218-234, 1999, J. Lipid
Res. 37 , 907-925, 1996, Curr.Opin.Lipidol. 10 ,
151-159, 1999). Thus, it is understood that the lipid metabolism is improved by promoting the expression of the PPARγ gene, and further, it has a preventive and therapeutic action for diabetes.

On the other hand, regarding the metabolism of carbohydrates in the body, in muscle and adipose tissue, glucose uptake is carried out via a glucose transporter (GLUT) on the cell membrane, and glucose depends on the amount of glucose transporter. The amount of uptake is defined. The main glucose transporter of these tissues is called glucose transporter 4 (GLUT4), but it is usually present inside the cell and moves (translocates) onto the cell membrane by insulin stimulation. It is taken into the cell through the carrier. In addition, it has been reported that transgenic mice in which GLUT4 is overexpressed even in a small amount are unlikely to become diabetic due to a high fat diet (Ikemoto, S. et al .: Proc. Natl. Acad.
Sci. USA, 92: 3086-3089, 1995), a material that promotes the expression of GLUT4 in tissues is considered effective for the prevention and cure of diabetes.

The insulin receptor plays a role in transmitting the insulin stimulation to the glucose transporter 4. In other words, the insulin receptor is one of tyrosine kinase-coupled receptors, and is a protein in which an α subunit that binds to insulin and a β subunit that penetrates the cell membrane and contains tyrosine kinase in the cytoplasm are linked by a disulfide bond. . The insulin receptor binds to insulin to initiate glucose uptake into cells and signal transduction that initiates glycogen synthesis. Insulin tyrosine kinase is activated by binding to the receptor and is autophosphorylated. Insulin receptor substrate 1 (IRS 1) binds to the phosphorylated tyrosine, and this IRS1 is phosphorylated. Phosphorylated IRS1 binds to and activates phosphatidylinositol (PI) -3-kinase (PI-3kinase). The activated PI-3 kinase further activates protein kinase B (PKB) by attracting it to the cell membrane. The activated PKB moves GLUT4 to the cell membrane and takes glucose into the cell. Therefore, a material that promotes the expression of the insulin receptor gene is considered to be effective in the prevention and cure of diabetes.

Against this backdrop, an extract of Rosaceae Fragaria L. containing tiliroside etc. improves fat metabolism such as PPARγ, aquaporin 7, adiponectin, GLUT4 and insulin receptor, and further prevents diabetes The present invention was completed by finding an action that promotes the expression of the gene to be expressed.
That is, an object of the present invention is to provide a novel fat metabolism gene expression promoter and diabetes prevention-related gene expression promoter that promotes the expression of genes such as aquaporin 7, PPARγ, adiponectin, GLUT4 and insulin receptor.

The features of the present invention for solving the above-described problems are as follows.
(1) A fat metabolism improving gene expression promoter comprising an extract of Rosaceae Fragaria L. as an active ingredient.
(2) The fat metabolism improving gene expression promoter according to (1) above, wherein the extract contains tyrilloside.
(3) The fat metabolism improving gene expression promoter according to (1) or (2) above, wherein seeds are used as a part of the Rosaceae Fragaria L.
(4) Diabetes prevention-related gene expression promoter comprising as an active ingredient an extract of Rosaceae Fragaria L.
(5) The diabetes prevention-related gene expression promoter according to (4), wherein the extract contains tyrilloside.
(6) The diabetes prevention-related gene expression promoter according to (4) or (5) above, wherein seeds are used as a part of the Rosaceae Fragaria L.
(7) A food or drink comprising the fat metabolism-improving gene expression promoter and the diabetes prevention-related gene expression promoter according to any one of (1) to (6) above.
(8) Skin for mammals including humans, comprising the fat metabolism improving gene expression promoter and the diabetes prevention related gene expression promoter according to any one of (1) to (6) above Topical agent.
(9) A pharmaceutical product for mammals including humans, comprising the fat metabolism improving gene expression promoter according to any one of (1) to (6) above and the diabetes prevention-related gene expression promoter. .
(10) A feed for mammals comprising the fat metabolism-improving gene expression promoter and the diabetes prevention-related gene expression promoter according to any one of (1) to (6) above.

The present invention is described in detail below.
The fat metabolism-improving gene expression promoter and the diabetes prevention-related gene expression promoter of the present invention (hereinafter simply referred to as “fatty metabolism-improving gene expression promoter” and the like) are referred to as Rosaceae Fragaria (Rosaceae Fragaria). L.) extract is an active ingredient.
The kind of Rosaceae Fragaria L. used as a raw material of the present invention is not particularly limited, and examples thereof include Fragaria daltoniana, Fragaria iinumae, Fragaria.
nilgerrensis, Fragaria nipponica (Shirobanana snake strawberry), Fragaria nipponica f. rosea (Safflower snake strawberry), Fragaria nipponica var.
viridis, Fragaria yezoensis, Fragaria moupinensis, Fragaria
orientalis, Fragaria moschata, Fragaria ×
ananassa DUCHESNE (Dutch strawberry), Fragaria chiloensis (Chile strawberry), Fragaria iturupensis Staudt, Fragaria virginiana (Virginia strawberry), Fragaria
× Potentilla (intergeneric hybrid), Fragaria × vescana, etc.
These may be used alone or in combination of two or more. Of these, Fragaria ×
Ananassa DUCHESNE (Netherlands strawberry) is preferred.

Fragaria used at this time ×
The cultivar of ananassa DUCHESNE (Dutch Strawberry) is not particularly limited. For example, Toyono, Nyoho, Tochiotome, Sahonoka, Akihime, Asuka Wave, Ascalbee, Iberry Chihime, Red Pearl, Sachinoka, Amaou, Hoho Seisei, Benihoppe Momoichigo, Natsumi, Summer Princess, Petika, Natsumusume (Karenya), Echigohime (Echigohime), etc. However, it is not limited to these. These may be used alone or in combination of two or more.

  The part of Rosaceae Fragaria L. used as a raw material is not particularly limited, but leaves, stems, fruits, flowers, seeds, etc. can be used, especially using seeds. preferable. This is because polyphenols such as tyrilloside are contained at a high concentration, thereby having an excellent gene expression for fat metabolism improvement and diabetes prevention.

  It is preferable that tiriloside is contained as a component of Rosaceae Fragaria L .. This is because it has an excellent effect of promoting expression of a fat metabolism improving gene and a diabetes prevention gene. Here, tiliroside means a compound represented by the following chemical formula (1).

  At this time, the content of tyrilloside is not particularly limited. However, when the total mass of the fat metabolism improving gene expression promoter and the like is 100% by mass, 0.01 to 15% by mass, preferably 0.5 to 10% by mass. It is preferable to do. This is because it has more excellent fat metabolism improving gene expression promoting action and diabetes prevention related gene expression promoting action.

  In addition, the production method of the fat metabolism improving gene expression promoter and the like is not particularly limited, but as a Rosaceae genus (Rosaceae Fragaria L.), a seed of Rosaceae (Rosaceae Fragaria L.) (hereinafter simply referred to as “ In the case of using “strawberry seeds”), polar solvent extraction, supercritical extraction and the like can be mentioned. In the present invention, only one of these may be used, or both of them may be used.

Here, when extracting with a polar solvent, a strawberry seed may be used as it is as an extraction raw material, but a defatted strawberry seed may be used. It is because an active ingredient can be extracted easily.
At this time, as a degreasing method, for example, the oil content may be separated by pressing strawberry seeds, or after separating the oil content, the residual oil content of the pressed product is extracted and separated with a degreasing solvent (fat-soluble organic solvent). You may do it. Furthermore, strawberry seeds may be pulverized and extracted and separated using a degreasing solvent (fat-soluble organic solvent).

  At this time, preferable degreasing solvents include n-hexane, acetone and the like. In particular, it is preferable to use n-hexane. This is because the extracted oil can be used as an edible oil and the defatted strawberry seed extract can be easily used as a food material. These degreasing solvents may be used alone or in combination of two or more.

  Furthermore, when extracting by polar solvent extraction, the polar solvent to be used is not particularly limited. For example, water, methanol, ethanol, isopropanol, acetone, 1,3-butylene glycol, ethylene glycol, propylene glycol, glycerin, acetic acid, acetic acid are used. Examples include ethyl, ether, hexane and the like. Of these, water and ethanol are preferred. In particular, it is preferable to use hydrous ethanol. These may be used alone or in combination of two or more.

  When water is used as the extraction solvent, the extraction temperature is 20 to 100 ° C., preferably about 80 to 100 ° C. This is because if the extraction temperature is too low, it is difficult to extract active ingredients. The kind of water for extraction is not particularly limited, and tap water, distilled water, mineral water, alkaline ionized water and the like can be used.

  When hydrous ethanol is used as the extraction solvent, the ethanol concentration is preferably 30 to 90 wt%. This is because if the amount is less than about 30 wt% or exceeds 90 wt%, the extraction amount of the active ingredient tends to decrease. The extraction temperature is 20 to 80 ° C, preferably about 50 to 80 ° C. In addition, the water-containing ethanol extraction may be repeated at various concentrations in order to improve the content of the active ingredient.

  In addition, when extracting with a polar solvent, any extraction method such as continuous extraction, immersion extraction, countercurrent extraction, etc. can be employed as the extraction method, and any apparatus can be used at room temperature or under reflux heating. Can do. Moreover, you may combine the said extraction method etc.

  As a specific method, an extraction raw material is put into a treatment tank filled with an extraction solvent, and an active ingredient is eluted while stirring. For example, when water or water-containing ethanol is used as the extraction solvent, the extraction is performed for about 30 minutes to 5 hours using a polar solvent of about 5 to 100 times (weight ratio) of the extraction raw material. The active ingredient is eluted in the solvent, and then filtered to remove the extraction residue to obtain an extract. Thereafter, the extract is subjected to treatments such as dilution, concentration, drying, and purification according to a conventional method to obtain a gene expression promoter for improving fat metabolism.

  Examples of the purification method include activated carbon treatment, resin adsorption treatment, ion exchange resin, liquid-liquid countercurrent distribution, and the like, but they are not used in large quantities when added to foods. It may be used unpurified.

  Moreover, when extracting by supercritical extraction, the supercritical fluid to be used is not specifically limited, For example, a carbon dioxide, water, etc. are mentioned. In addition, these may use only 1 type and may use 2 or more types together. Of these, carbon dioxide is particularly preferred. It is because an active ingredient can be extracted more easily. The extraction method at this time may be performed by a known method.

  The fat metabolism improving gene expression promoter of the present invention can be used as a material for various foods and drinks. Examples of food and drink include edible oil (salad oil), confectionery (gum, candy, caramel, chocolate, cookie, snack, jelly, gummy, tablet confection etc.), noodles (soba, udon, ramen etc.), dairy products ( Milk, ice cream, yogurt, etc.), seasonings (miso, soy sauce, etc.), soups, beverages (juice, coffee, tea, tea, carbonated drinks, sports drinks, etc.) and health foods (tablets , Capsules, etc.) and nutritional supplements (nutrient drinks, etc.). The food / beverage products may be appropriately mixed with the fat metabolism improving gene expression promoter of the present invention.

  These foods and drinks can be blended with various ingredients depending on the type, for example, glucose, fructose, sucrose, maltose, sorbitol, stevioside, corn syrup, lactose, citric acid, tartaric acid, malic acid, succinic acid. Acid, lactic acid, L-ascorbic acid, dl-α-tocopherol, sodium erythorbate, glycerin, propylene glycol, glycerin fatty acid ester, polyglycerin fatty acid ester, sucrose fatty acid ester, sorbitan fatty acid ester, propylene glycol fatty acid ester, gum arabic, Food materials such as carrageenan, casein, gelatin, pectin, agar, vitamin Bs, nicotinic acid amide, calcium pantothenate, amino acids, calcium salts, pigments, fragrances and preservatives can be used. In addition, this fat metabolism improving gene expression promoter with health maintenance function includes other antioxidants and health food ingredients such as antioxidants, reduced ascorbic acid (vitamin C), vitamins E, reduced glutatin, tocotrienol, vitamin A derivative, lycopene, β-cryptoxanthin, astaxanthin, zeaxanthin, fucoxanthin, uric acid, ubiquinone, coenzyme Q10, folic acid, garlic extract, allicin, sezamin, lignans, catechin, isoflavone, chalcone , Tannins, flavonoids, coumarin, isocoumarins, blueberry extract, arbutin, tannin, anthocyanin, apple polyphenol, grape seed extract, ellagic acid, kojic acid, surge extract health food material, V. (vitamins) A, V. B1, V.B2, V.B6, V.B12 , VC, VD, VE, VP, choline, niacin, pantothenic acid, calcium folate, EPA, oligosaccharide, dietary fiber, squalene, soy lecithin, taurine, donariella, protein, octacosanol, DHA, egg yolk lecithin, linoleic acid, lactoferrin, Magnesium, zinc, chromium, selenium, potassium, heme iron, oyster meat extract, chitosan, chitin oligosaccharide, collagen, chondroitin, turmeric, licorice, kokushi, keihi, hawthorn, ginger, ganoderma, rainbow trout extract, suppon, licorice, wolfberry , Keihi, hawthorn, ginger, reishi, plantain, chamomile, chamomile, dandelion, hibiscus, honey, boren, royal jelly, lime, lavender, rosehip, rosemary, sage, bifidobacteria, faecalis, lacris, small Germ oil, sesame oil, perilla oil, soybean oil, medium chain fatty acid, agaricus, ginkgo biloba extract, turmeric, chondroitin, brown rice germ extract, litchi, onion, DHA, EPA, DPA, strawberry tea, cordyceps, garlic, bee, papaya , Puaru, Propolis, Meguri Tree, Yabushake, Royal Jelly, Saw Palmetto, Hyaluronic Acid, Collagen, Gabba, Harpseal Oil, Shark Cartilage, Glucosamine, Lecithin, Phosphatidylserine, Padlock Carrot, Mulberry Leaf, Soybean Extract, Echinacea, Ezoukogi, barley extract, olive leaf, olive fruit, Gymnema, banaba, Salacia, Garcinia, chitosan, St. John's wort, jujube, carrot, passion flower, broccoli, placenta, pearl barley, grape seed, peanut seed coat, bilberry, black Kohosh, Maria Thistle, Laurel, Sage, Rosemary, Raffma, Black Vinegar, Goya, Maca, Safflower, Flax, Oolong Tea, Flower Thorn, Caffeine, Capsaicin, Xylooligosaccharide, Glucosamine, Buckwheat, Citrus, Dietary Fiber, Protein, Prunes , Spirulina, Barley Young Leaves, Nucleic Acid, Yeast, Shiitake Mushroom, Plum Meat, Amino Acid, Deep Sea Mushroom Extract, Noni, Oyster Meat, Suppon, Champignon, Plantain, Acerola, Pineapple, Banana, Peach, Apricot, Melon, Strawberry, Raspberry, Orange , Fucoidan, Meshimakobu, Cranberry, Chondroitin sulfate, Zinc, Iron, Ceramide, Silk peptide, Glycine, Niacin, Chesttree, Ceramide, L-cysteine, L-carnitine, Red wine leaf, Millet, Horsetail, Biotin, Centella Asiatica , Hasuka Pycnogenol, Japanese cypress, rhubarb, clove, rosemary, catechin, puer, citric acid, brewer's yeast, merilot, black zinger, ginger, gadget, nattokinase, benichouji, tocotrienol, lactoferrin, cinnamon, buckwheat, cocoa, yuzu seed extract , Perilla seed extract, lychee seed extract, evening primrose extract, black rice extract, α-lipoic acid, gabba, fresh coffee bean extract, buffalo extract, kiwi seed extract, Unshu mandarin orange extract, red ginger extract, astaxanthin) it can.

  As a specific production method, the fat metabolism improving gene expression promoter of the present invention is used as it is, and in the case of an extract, it is spray-dried or freeze-dried together with powdered dextrin, and this is converted into powder, granules, tablets or solutions It can be easily contained in foods (instant foods, etc.). If necessary, it can also be mixed with a binder such as gum arabic to form a powder or granules, and added to a solid food. In the case of an extract, it can also be added to a beverage as it is or after being dispersed and dissolved in water, ethanol, glycerin or a mixture thereof.

  The fat metabolism improving gene expression promoter or the like of the present invention may be used as a raw material for drugs (including pharmaceuticals and quasi drugs). It can be produced by appropriately blending the fat metabolism improving gene expression promoter of the present invention with a raw material for a pharmaceutical preparation. In addition, the said chemical | medical agent may be used for a human and may be used for mammals other than a human. Examples of the raw material for preparation that can be blended in the fat metabolism improving gene expression promoter of the present invention include, for example, excipients (glucose, lactose, sucrose, sodium chloride, starch, calcium carbonate, crystalline cellulose, cacao butter, hydrogenated vegetable oil, kaolin , Talc, etc.), binder (distilled water, physiological saline, ethanol water, simple syrup, glucose solution, starch solution, gelatin solution, carboxymethylcellulose, potassium phosphate, polyvinylpyrrolidone, etc.), disintegrant (sodium alginate, agar, Sodium bicarbonate, calcium carbonate, sodium lauryl sulfate, stearic acid monoglyceride, starch, lactose, gum arabic powder, gelatin, ethanol, etc.), disintegration inhibitors (sucrose, stearin, cocoa butter, hydrogenated oil, etc.), absorption enhancers ( Quaternary ammonium base, sodium lauryl sulfate Beam, etc.), adsorbents (glycerin, starch, lactose, kaolin, bentonite, silicic acid, etc.), lubricants (purified talc, stearates, polyethylene glycol, and the like) and the like.

  The administration method of the fat metabolism improving gene expression promoter and the like according to the present invention can generally be administered orally in the form of tablets, pills, soft / hard capsules, fine granules, powders, granules and the like. . The water-soluble preparation can be administered orally as a liquid. Furthermore, parenteral administration may be used. When administered as a parenteral agent, the fat metabolism improving gene expression promoter of the present invention is dispersed in an appropriate solubilizer such as ethanol or water, and then a poultice, lotion, ointment, tincture, cream It can be applied in a dosage form. In addition, the water-soluble preparations such as the gene expression promoter for improving fat metabolism can be used as it is or with a dispersing agent, suspending agent, stabilizer, etc. added to a poultice, lotion, ointment, tincture, cream. It can be applied in a dosage form.

  The dose may vary depending on the administration method, medical condition, age of the patient, etc., but for adults, it can be generally administered in an amount of about 5 to 200 mg as an active ingredient per day and usually about 0.5 to 100 mg for children.

  The compounding ratio when the fat metabolism improving gene expression promoter of the present invention is used as a drug can be appropriately changed depending on the dosage form, but is usually about 0. 0 when administered orally or by mucosal absorption. In the case of 01 to 10 wt% and parenteral administration, about 0.01 to 20 wt% is recommended. In addition, since the dose varies depending on various conditions, a dose smaller than the above dose may be sufficient, or it may be necessary to administer beyond the range. The pharmaceutical composition may include other known compounds commonly used in the pharmaceutical field, and compounds necessary for molding into a form suitable for oral administration, in addition to the above-described fat metabolism improving gene expression promoter and the like. Good. Examples of such compounds include lactose, starch, hydroxypropyl cellulose, kaolin, talc, calcium carbonate and the like.

Moreover, the fat metabolism improvement gene expression promoter of this invention etc. can be contained in the animal feed for mammals. The animal feed can be contained in the same manner as the food and drink. The animal feed is not particularly limited. For example, it is used for domestic animals such as cattle and pigs, companion animals such as dogs, cats and hamsters (animals kept as pets). can do.
For example, flour, meat, etc. can be used as companion animal feed. At this time, examples of the flour include wheat flour, rice flour, rye flour, corn flour, millet flour, bubble flour, corn flour, and soybean flour, and these flours may be used in combination of two or more. By using flour, nutrients such as carbohydrates can be supplied to companion animals. Among the above flours, it is most preferable to use flour, and as flour, strong flour, medium flour, thin flour can be used alone or in combination, and even when such flour and other flour are used in combination Good. Furthermore, in order to adjust the elasticity of the animal feed after the heat treatment, wheat flour, wheat gluten, soybean protein and the like may be combined. In addition, the network structure derived from gluten contained in wheat flour can constitute a puffed tissue structure when heat-treated, which contributes to improving the texture.

  The meat used in the present invention is not particularly limited, and chicken, pork, beef, mutton, goat meat, salmon meat, turkey meat, horse meat, etc. can be used, but chicken is preferably used in terms of flavor. The The above meat is obtained by slaughtering and demolishing livestock in the usual way. In addition, since the deterioration of the quality of a product with intermediate moisture or low moisture is mainly caused by fat oxidation, the meat to be used is preferably red meat from which the fat content is low or fat is removed. In addition, the coexistence of meat can improve the palatability of companion animals as well as strengthening high-quality animal proteins.

Even if the fat metabolism improving gene expression promoter of the present invention is used as an external skin preparation (including cosmetics, pharmaceuticals and quasi drugs), it has a fat metabolism improving gene expression promoting action and a diabetes prevention related gene expression promoting action. You can expect. In addition, the said skin external preparation may be used for a human and may be used for mammals other than a human.
Examples of the external preparation for skin to which the fat metabolism improving gene expression promoter of the present invention can be blended include, for example, milky lotion, soap, facial cleanser, bath preparation, cream, milky lotion, lotion, eau de cologne, shaving cream, whiskers. Shaving lotion, cosmetic oil, suntan / sunscreen lotion, powder, foundation, perfume, pack, nail cream, enamel, enamel remover, eyebrow, blusher, eye cream, eye shadow, mascara, eyeliner, lipstick, lip balm Shampoos, rinses, hair dyes, dispersions, cleaning agents and the like.
Examples of the form of pharmaceuticals or quasi-drugs to which the fat metabolism improving gene expression promoter of the present invention can be blended include ointments, creams, and liquids for external use.

In addition to the fat metabolism improving gene expression promoting agent according to the present invention, the external preparation for skin of the above form includes cosmetics, quasi-drugs and the like as long as the fat metabolism improving gene expression promoting action and the diabetes prevention related gene expression promoting action are not impaired. Ingredients, oils, higher alcohols, fatty acids, UV absorbers, powders, pigments, surfactants, polyhydric alcohols / sugars, polymers, bioactive ingredients, solvents, antioxidants , Fragrances, preservatives and the like can be blended.
Examples are listed below, but the present invention is not limited to these examples.

(1) Examples of oil components Ester-based oil phase components: glyceryl tri-2-ethylhexanoate, cetyl 2-ethylhexanoate, isopropyl myristate, butyl myristate, isopropyl palmitate, ethyl stearate, octyl palmitate, isostearic acid Isocetyl, butyl stearate, butyl myristate, ethyl linoleate, isopropyl linoleate, ethyl oleate, isocetyl myristate, isostearyl myristate, isostearyl palmitate, octyldodecyl myristate, isocetyl isostearate, diethyl sebacate, adipine Diisopropyl acid, isoaralkyl neopentanoate, glyceryl tri (capryl / caprate), trimethylolpropane tri-2-ethylhexanoate, trimethylol triisostearate Propane, pentaerythritol tetra-2-ethylhexanoate, cetyl caprylate, decyl laurate, hexyl laurate, decyl myristate, myristyl myristate, cetyl myristate, stearyl stearate, decyl oleate, cetyl ricinoleate, isolaurate Stearyl, isotridecyl myristate, isocetyl myristate, isostearyl myristate, isocetyl palmitate, isostearyl palmitate, octyl stearate, isocetyl stearate, isodecyl oleate, octyldodecyl linoleate, octyldodecyl isoleate, isopropyl isostearate Cetostearyl 2-ethylhexanoate, stearyl 2-ethylhexanoate, hexyl isostearate, ethyleneglycol dioctanoate , Ethylene glycol dioleate, propylene glycol dicaprate, propylene glycol di (capryl / capric acid), propylene glycol dicaprylate, neopentyl glycol dicaprate, neopentyl glycol dioctanoate, glyceryl tricaprylate, glyceryl triundecylate, triisopalmitine Glyceryl acid, glyceryl triisostearate, octyldodecyl neopentanoate, isostearyl octanoate, octyl isononanoate, hexyl decyl neodecanoate, octyldodecyl neodecanoate, isocetyl isostearate, isostearyl isostearate, octyldecyl isostearate, polyglycerin oleic acid Ester, polyglycerol isostearate, dipropyl carbonate, charcoal Dialkyl (C12-18), triisocetyl citrate, triisoaralkyl citrate, triisooctyl citrate, lauryl lactate, myristyl lactate, cetyl lactate, octyl decyl lactate, triethyl citrate, acetyl triethyl citrate, acetyl tributyl citrate, Trioctyl citrate, diisostearyl malate, 2-ethylhexyl hydroxystearate, di-2-ethylhexyl succinate, diisobutyl adipate, diisopropyl sebacate, dioctyl sebacate, cholesteryl stearate, cholesteryl isostearate, cholesteryl hydroxystearate, olein Cholesteryl acid, dihydrocholesteryl oleate, phytosteryl isostearate, phytosteryl oleate, 12-stearoyl hydroxystearate Cetyl, 12-stearoyl-hydroxystearic acid stearyl 12-stearoyl-hydroxystearic acid isostearate, and the like.
Hydrocarbon oil phase components: squalane, liquid paraffin, α-olefin oligomer, isoparaffin, ceresin, paraffin, liquid isoparaffin, polybutene, microcrystalline wax, petrolatum and the like.
Animal and vegetable oils and their hydrogenated oils, and naturally occurring waxes: beef tallow, hydrogenated beef tallow, lard, hydrogenated tallow, horse oil, hydrogenated horse oil, mink oil, orange luffy oil, fish oil, hydrogenated fish oil, egg yolk oil and other animal oils and Its hardened oil, avocado oil, almond oil, olive oil, cacao butter, kiwi seed oil, apricot oil, kukui nut oil, sesame oil, wheat germ oil, rice germ oil, rice bran oil, safflower oil, shea butter, soybean oil, evening primrose oil , Perilla oil, tea seed oil, camellia oil, corn oil, rapeseed oil, hydrogenated rapeseed oil, palm kernel oil, hydrogenated palm kernel oil, palm oil, hydrogenated palm oil, peanut oil, hydrogenated peanut oil, castor oil, hydrogenated castor oil , Vegetable oils such as sunflower oil, grape seed oil, jojoba oil, hardened jojoba oil, macadamia nut oil, medhome oil, cottonseed oil, hardened cottonseed oil, coconut oil, hardened coconut oil and its hardened , Beeswax, high acid value beeswax, lanolin, reduced lanolin, hydrogenated lanolin, liquid lanolin, carnauba wax and montan wax.
Silicone oil phase components: dimethylpolysiloxane, methylphenylpolysiloxane, methylcyclopolysiloxane, octamethylpolysiloxane, decamethylpolysiloxane, dodecamethylcyclosiloxane, methylhydrogenpolysiloxane, polyether-modified organopolysiloxane, dimethyl Siloxane / methylcetyloxysiloxane copolymer, dimethylsiloxane / methylstearoxysiloxane copolymer, alkyl-modified organopolysiloxane, terminal-modified organopolysiloxane, amino-modified silicone oil, amino-modified organopolysiloxane, dimethiconol, silicone gel, acrylic Examples include silicone, trimethylsiloxysilicic acid, and silicone RTV rubber.
Fluorine oil phase components: perfluoropolyether, fluorine-modified organopolysiloxane, fluorinated pitch, fluorocarbon, fluoroalcohol, fluoroalkyl / polyoxyalkylene co-modified organopolysiloxane, and the like.

(2) Examples of higher alcohols Lauryl alcohol, myristyl alcohol, cetyl alcohol, stearyl alcohol, isostearyl alcohol, oleyl alcohol, behenyl alcohol, 2-ethylhexanol, hexadecyl alcohol, octyldodecanol and the like can be mentioned.

(3) Examples of fatty acids Caprylic acid, capric acid, undecylenic acid, lauric acid, myristic acid, palmitic acid, palmitoleic acid, stearic acid, isostearic acid, oleic acid, linoleic acid, linolenic acid, arachidic acid, arachidonic acid, behenic acid , Erucic acid, 2-ethylhexanoic acid and the like.

(4) Examples of UV absorbers Paraaminobenzoic acid, amyl paraaminobenzoate, ethyldihydroxypropyl paraaminobenzoate, glyceryl paraaminobenzoate, ethyl paraaminobenzoate, octyl paraaminobenzoate, octyldimethyl paraaminobenzoate, ethylene glycol salicylate, salicylic acid Octyl, triethanolamine salicylate, phenyl salicylate, butylphenyl salicylate, benzyl salicylate, homomenthyl salicylate, benzyl cinnamate, octyl paramethoxycinnamate, 2-ethylhexyl paramethoxycinnamate, mono-2-diparamethoxycinnamate Glyceryl ethylhexanoate, isopropyl paramethoxycinnamate, diethanolamine salt of paramethoxyhydrocinnamic acid, diisopropyl diisopropylcinnamic acid Stealth mixture, urocanic acid, ethyl urocanate, hydroxymethoxybenzophenone, hydroxymethoxybenzophenone sulfonic acid and its salts, dihydroxymethoxybenzophenone, dihydroxymethoxybenzophenone sodium disulfonate, dihydroxybenzophenone, dihydroxydimethoxybenzophenone, hydroxyoctoxybenzophenone, tetrahydroxybenzophenone, Butylmethoxydibenzoylmethane, 2,4,6-trianilino-p- (carbo-2-ethylhexyl-1-oxy) -1,3,5-triazine, 2- (2-hydroxy-5-methylphenyl) benzotriazole , Methyl-O-aminobenzoate, 2-ethylhexyl-2-cyano-3, 3-diphenyl acrylate, phenylbenzimidazole sulfate, 3- (4-methylbenzylidene) can Examples include full, isopropyldibenzoylmethane, 4- (3,4-dimethoxyphenylmethylene) -2, 5-dioxo-1-imidazolidinepropionate 2-ethylhexyl, and the like, polymer derivatives, silane derivatives, and the like.

(5) Examples of powders and pigments Red 104, Red 201, Yellow 4, Blue 1, Black 401 and other dyes, Yellow 4 AL lake, Yellow 203 BA lake and other lake dyes, nylon powder , Silk powder, urethane powder, Teflon (registered trademark) powder, silicone powder, polymethyl methacrylate powder, cellulose powder, starch, silicone elastomer spherical powder, polyethylene powder, yellow iron oxide, red iron oxide, black Colored pigments such as iron oxide, chromium oxide, carbon black, ultramarine and bitumen, white pigments such as zinc oxide, titanium oxide and cerium oxide, extender pigments such as talc, mica, sericite, kaolin and barium sulfate plate, titanium mica Pearl pigments such as barium sulfate, calcium carbonate, magnesium carbonate, aluminum silicate, metal salts such as magnesium silicate, Inorganic powders such as Rica and alumina, metal soaps such as aluminum stearate, magnesium stearate, zinc palmitate, zinc myristate, magnesium myristate, zinc laurate, zinc undecylenate, bentonite, smectite, boron nitride, etc. It is done. There are no particular restrictions on the shape of these powders (spherical, rod-like, needle-like, plate-like, irregular shape, flake-like, spindle-like, etc.) and particle diameter. These powders are conventionally known surface treatments such as fluorine compound treatment, silicone treatment, silicone resin treatment, pendant treatment, silane coupling agent treatment, titanium coupling agent treatment, oil agent treatment, N-acylated lysine treatment, The surface treatment may or may not be performed in advance by polyacrylic acid treatment, metal soap treatment, amino acid treatment, lecithin treatment, inorganic compound treatment, plasma treatment, mechanochemical treatment or the like.

(6) Examples of surfactants Anionic surfactants: fatty acid soap, α-acyl sulfonate, alkyl sulfonate, alkyl allyl sulfonate, alkyl naphthalene sulfonate, alkyl sulfate, POE alkyl ether sulfate , Alkylamide sulfate, alkyl phosphate, POE alkyl phosphate, alkylamide phosphate, alkyloylalkyl taurine salt, N-acyl amino acid salt, POE alkyl ether carboxylate, alkyl sulfosuccinate, alkyl sulfoacetic acid Sodium, acylated hydrolyzed collagen peptide salt, perfluoroalkyl phosphate, etc. are mentioned.
Cationic surfactant: alkyltrimethylammonium chloride, stearyltrimethylammonium chloride, stearyltrimethylammonium bromide, cetostearyltrimethylammonium chloride, distearyldimethylammonium chloride, stearyldimethylbenzylammonium chloride, behenyltrimethylammonium bromide, benzalkonium chloride , Behenic acid amidopropyldimethylhydroxypropylammonium chloride, stearic acid diethylaminoethylamide, stearic acid dimethylaminopropylamide, lanolin derivative quaternary ammonium salts, and the like.
Amphoteric surfactants: carboxybetaine type, amide betaine type, sulfobetaine type, hydroxysulfobetaine type, amide sulfobetaine type, phosphobetaine type, aminocarboxylate type, imidazoline derivative type, amidoamine type and the like.
Nonionic surfactant: Propylene glycol fatty acid ester, glycerin fatty acid ester, polyglycerin fatty acid ester, sorbitan fatty acid ester, POE sorbitan fatty acid ester, POE sorbit fatty acid ester, POE glycerin fatty acid ester, POE alkyl ether, POE fatty acid ester, POE cured castor Oil, POE castor oil, POE / POP copolymer, POE / POP alkyl ether, polyether-modified silicone lauric acid alkanolamide, alkylamine oxide, hydrogenated soybean phospholipid, and the like.
Natural surfactant: lecithin, saponin, sugar surfactant and the like.

(7) Examples of polyhydric alcohols and sugars Ethylene glycol, diethylene glycol, polyethylene glycol, propylene glycol, dipropylene glycol, polypropylene glycol, glycerin, diglycerin, polyglycerin, 3-methyl-1,3-butanediol, 1, 3 -Butylene glycol, sorbitol, mannitol, raffinose, erythritol, glucose, sucrose, fructose, xylitol, lactose, maltose, maltitol, trehalose, alkylated trehalose, mixed isomerized sugar, sulfated trehalose, pullulan and the like. These chemically modified compounds can also be used.

(8) Examples of polymers Acrylic ester / methacrylic acid ester copolymer (plus size, manufactured by Kyoyo Chemical), vinyl acetate / crotonic acid copolymer (resin 28-1310, manufactured by NSC), vinyl acetate / croton Acid / vinyl neodecanate copolymer (28-2930, manufactured by NSC), methyl vinyl ether maleic acid half ester (Gantrez ES, manufactured by ISP), T-butyl acrylate / ethyl acrylate / methacrylic acid copolymer (rubymer) , BASF), vinyl pyrrolidone / vinyl acetate / vinyl propionate copolymer (Rubicol VAP, BASF), vinyl acetate / crotonic acid copolymer (Rubiset CA, BASF), vinyl acetate / croton Acid / vinyl pyrrolidone copolymer (Rubiset CAP, manufactured by BASF), vinyl pyrrolidone / acrylate copolymer (Rubiflex, BA SF), acrylate / acrylamide copolymer (Ultrahold, BASF), vinyl acetate / butyl maleate / isobornyl acrylate copolymer (Advantage, ISP), carboxy vinyl polymer (Carbopol, BF Goodrich), anionic polymer compounds such as acrylic acid / alkyl methacrylate copolymers (Pemulene, BF Goodrich) and acetic acid amphoteric compounds of dialkylaminoethyl methacrylate polymers (Yukaformer, Mitsubishi Chemical) Amphoteric polymer compounds such as octyl acrylate acrylate / hydroxypropyl acrylate / butyl aminoethyl methacrylate copolymer (AMPHOMER, NSC), quaternized vinylpyrrolidone / dimethylaminoethyl methacrylate (GAFQUAT, ISP) , Methyl vinyl imidazolium chloride Cationic polymer compounds such as vinyl / vinylpyrrolidone copolymer (rubicoat, manufactured by BASF), polyvinylpyrrolidone (rubiscol K, manufactured by BASF), vinylpyrrolidone / vinyl acetate copolymer (rubiscol VA, manufactured by BASF) ), Nonionic polymer compounds such as vinylpyrrolidone / dimethylaminoethyl methacrylate copolymer (copolymer 937, manufactured by ISP), vinylcaprolactam / vinylpyrrolidone / dimethylaminoethyl methacrylate copolymer (copolymer VC713, manufactured by ISP), etc. There is. Cellulose or derivatives thereof, keratin and collagen or derivatives thereof, calcium alginate, pullulan, agar, gelatin, tamarind seed polysaccharide, xanthan gum, carrageenan, high methoxyl pectin, low methoxyl pectin, guar gum, gum arabic, crystalline cellulose, arabino Naturally derived polymer compounds such as galactan, gum karaya, gum tragacanth, alginic acid, albumin, casein, curdlan, gellan gum and dextran can also be suitably used.

(9) Examples of physiologically active ingredients Examples of physiologically active ingredients include substances that impart some physiological activity to the skin when applied to the skin. For example, whitening ingredients, immunostimulants, anti-aging agents, UV protection agents, slimming agents, tanning agents, antioxidants, hair growth agents, hair restorers, moisturizers, blood circulation promoters, antibacterial agents, bactericides, desiccants, A cooling sensation agent, a warming sensation agent, vitamins, an amino acid, a wound healing promoter, an irritation relaxation agent, an analgesic agent, a cell activator, an enzyme component, etc. are mentioned. Examples of these suitable ingredients include, for example, ashitaba extract, avocado extract, amateur extract, altea extract, arnica extract, aloe extract, apricot extract, apricot kernel extract, ginkgo biloba extract, fennel extract, turmeric extract, oolong tea extract, ages Extract, Echinacea leaf extract, Ogon extract, Oat extract, Oen extract, Barley extract, Hypericum extract, Oyster extract, Dutch mustard extract, Orange extract, Seawater dried product, Seaweed extract, Hydrolyzed elastin, Hydrolyzed wheat powder, Hydrolyzed silk , Chamomile extract, Carrot extract, Kawara mugwort extract, Licorice extract, Calcade extract, Oyster extract, Kina extract, Cucumber extract, Guanosine, Gardenia extract, Kumazasa extract, Clarae Kiss, walnut extract, grapefruit extract, clematis extract, chlorella extract, mulberry extract, gentian extract, tea extract, yeast extract, burdock extract, fermented rice bran extract, rice germ oil, comfrey extract, collagen, bilberry extract, saicin extract, psycho extract Extract Kizuta extract, hawthorn extract, elderberry extract, yarrow extract, mint extract, sage extract, mallow extract, senki Sue extract, assembly extract, soybean extract, tiso extract, thyme extract, tea extract, clove extract, chigaya extract, chimpi extract, touki extract, toshinsen extract, tonin extract, spruce extract, dokudami extract, tomato extract, natto extract, carrot extract, garlic extract, Novara extract, hibiscus extract, bacmond extract, parsley extract, honey, hamamelis extract, parietalia extract, toad extract, bisabolol, loquat extract, dandelion extract, burdock extract, bukuro extract, butcher bloom extract, grape extract, propolis, loofah extract, Safflower extract, peppermint extract, bodaige extract, button extract, hop extract, pine extract, marronnier extract, mizubasho Kiss, Mukuroji extract, Melissa extract, Peach extract, Cornflower extract, Eucalyptus extract, Yukinoshita extract, Yokuinin extract, Artemisia extract, Lavender extract, Apple extract, Lettuce extract, Lemon extract, Lotus root extract, Rose extract, Rosemary extract, Roman chamomile extract And royal jelly extract.
Biopolymers such as deoxyribonucleic acid, mucopolysaccharide, sodium hyaluronate, sodium chondroitin sulfate, collagen, elastin, chitin, chitosan, hydrolyzed eggshell membranes, amino acids, hydrolyzed peptides, sodium lactate, urea, sodium pyrrolidonecarboxylate , Moisturizing ingredients such as betaine, whey, trimethylglycine, oily ingredients such as sphingolipid, ceramide, phytosphingosine, cholesterol, cholesterol derivatives, phospholipids, ε-aminocaproic acid, glycyrrhizic acid, β-glycyrrhetinic acid, lysozyme chloride, guaiazulene, Immunostimulants such as hydrocortisone, vitamin A, vitamin B2, vitamin B6, vitamin C, vitamin D, vitamin E, calcium pantothenate, biotin, nicotinamide, vitamin C ester Vitamins, active ingredients such as allantoin, diisopropylamine dichloroacetate, 4-aminomethylcyclohexanecarboxylic acid, antioxidants such as tocopherol, carotenoid, flavonoid, tannin, lignan, saponin, α-hydroxy acid, β-hydroxy acid, etc. Cell activators, blood circulation promoters such as γ-oryzanol and vitamin E derivatives, wound healing agents such as retinol and retinol derivatives, arbutin, kojic acid, placenta extract, sulfur, ellagic acid, linoleic acid, tranexamic acid, glutathione, etc. Whitening agent, cephalanthin, licorice extract, red pepper tincture, hinokitiol, garlic iodide extract, pyridoxine hydrochloride, DL-α-tocopherol, DL-α-tocopherol acetate, nicotinic acid, nicotinic acid derivative, calcium pantothenate, D-pan Tothenyl alcohol, acetyl pantothenyl ethyl ether, biotin, allantoin, isopropylmethylphenol, estradiol, ethinyl estradiol, capronium chloride, benzalkonium chloride, diphenhydramine hydrochloride, takanal, camphor, salicylic acid, nonyl acid vanillylamide, nonanoic acid vanillylamide, pyroctone Olamine, glyceryl pentadecanoate, L-menthol, mononitroguaiacol, resorcin, γ-aminobutyric acid, benzethonium chloride, mexiletine hydrochloride, auxin, female hormone, cantalis tincture, cyclosporine, zinc pyrithione, hydrocortisone, minoxidil, monostearic acid Examples include hair growth agents such as polyoxyethylene sorbitan, mint oil, and Sasanishiki extract.

(10) Examples of antioxidants Sodium bisulfite, sodium sulfite, erythorbic acid, sodium erythorbate, dilauryl thiodipropionate, tocopherol, tolyl biguanide, nordihydroguaiaretic acid, parahydroxyanisole, butylhydroxyanisole, dibutylhydroxy Examples include plant extracts having an antioxidant effect such as toluene, ascorbyl stearate, ascorbyl palmitate, octyl gallate, propyl gallate, carotenoid, flavonoid, tannin, lignan, saponin, apple extract and clove extract.

(11) Examples of solvents Purified water, ethanol, lower alcohol, ethers, LPG, fluorocarbon, N-methylpyrrolidone, fluoroalcohol, volatile linear silicone, next-generation chlorofluorocarbon and the like.

Example 1
Production of Fat Metabolism Improvement Gene Expression Promoter, etc. (Strawberry Seed Extract) The ground strawberry seeds were defatted with hexane and then extracted with stirring with 70% ethanol (70 ° C., 1 hour). Thereafter, the obtained extract was concentrated and dried to obtain strawberry seed extract powder (fatty metabolism improving gene expression promoter and the like).
The polyphenol content was determined by HPLC using the foreign dennis method, and the tyriloside content was determined by HPLC under the following conditions. As a result, the polyphenol content (gallic acid equivalent) of the strawberry seed extract of this example was 10.8%, and tiliroside was 2.1%.

HPLC conditions Eluent: 37.5% acetonitrile Flow rate: 1
mL
Detection: UV 254 nm
Column: Shiseido capcelpack C18 (4.6 × 250 mm)

Example 2 and Example 3
As Example 2, tiliroside (manufactured by Extrasynthese SA) was used, and as Example 3, kaempferol 3-O-glucoside (manufactured by Extrasynthese SA) was used.

Test example (Example 1)
A mouse (ddY, male, 10 weeks old) is allowed to freely consume a high fat diet (High Fat Diet 32, Nippon Claire) and the strawberry seed extract of this example (10 or 50 mg / kg) once a day Orally administered. After 8 days, the animals were fasted for 18 hours, and blood was collected and organs (collateral testicles) were removed. The effect on each gene (AQP7, Adipo, PPARγ, GLUT4, Insr) expression was evaluated by RT-PCR using the accessory testicular fat cDNA. As comparative examples, mice of the same type as the above mice were allowed to freely eat a normal diet for 8 days (normal) and also a high fat diet (High Fat Diet 32, Clea Japan), and The same test was conducted on the control (control) obtained by oral administration of water in this example.

  A significant increase in the expression of AQP7 was observed at 10 mg / kg of strawberry seed extract (Fig. 1). Strawberry seed extract also showed a tendency to increase the expression of adiponectin and PPARγ involved in insulin resistance (Figs. 2 and 3). Furthermore, an increase in the expression of insulin receptor as a signal transduction enzyme and glucose transporter 4 (GLUT4) as a glucose transporter that initiates the uptake of glucose into cells was also observed (FIGS. 4 and 5). From the above, it was confirmed that the strawberry seed extract has anti-obesity and anti-diabetic effects.

Test Example 2 (Example 2 and Example 3)
For the tiliroside of Example 2 and kaempferol 3-O-glucoside of Example 3, Lpin1 (Fig. 6), PPARα (Fig. 7), CPT1 (Fig. 8), ACOX1 (Fig. 9), PPARγ (FIG. 10), Insr (FIG. 11) GLUT4 (FIG. 12), and Adipo (FIG. 13) were tested for gene expression. The results are shown in FIGS.

As a result of the experiment, kaempferol 3-0-glucoside showed a dose-dependent increase in expression of Lipin1 and PPARα genes in the liver (FIGS. 6 and 7). However, no such effect was observed in tiliroside. In CPT1 and ACOX1, neither expression was significantly enhanced. On the other hand, in fat, expression promoting action was recognized in both cases (FIGS. 8 and 9). Although the doses are different, it is not possible to make a general comparison, but it is thought that tiliroside works effectively in fat.

Although the compounding example of the fat metabolism improvement gene expression promoter of this invention etc. (strawberry seed extract) is given to the following, the following compounding example does not limit this invention.
Formulation Example 1: Chewing gum Sugar 53.0 wt%
Gum base 20.0
Glucose 10.0
Minamata 16.0
Fragrance 0.5
Strawberry seed extract 0.5
100.0wt%

Formulation Example 2: Gummy
Reduced water tank 40.0wt%
Granulated sugar 20.0
Glucose 20.0
Gelatin 4.7
Water 9.68
Strawberry juice 4.0
Grape flavor 0.6
Dye 0.02
Strawberry seed extract 1.0
100.0wt%

Formulation Example 3: Candy
50.0 wt% sugar
Minamata 33.0
Water 14.4
Organic acid 2.0
Fragrance 0.2
Strawberry seed extract 0.4
100.0wt%

Formulation Example 4: Yogurt (hard / soft)
Milk 41.5wt%
Nonfat dry milk 5.8
Sugar 8.0
Agar 0.15
Gelatin 0.1
Lactic acid bacteria 0.005
Strawberry seed extract 0.4
Perfume
Water residue
100.0wt%

Formulation Example 5: Soft drink
Fructose glucose liquid sugar 30.0wt%
Emulsifier 0.5
Strawberry seed extract 0.05
Perfume
Purified water residue
100.0wt%

Formulation Example 6: Tablets
76.4 wt% sugar
Glucose 19.0
Sucrose fatty acid ester 0.2
Strawberry seed extract 0.5
Purified water 3.9
100.0wt%

Formulation Example 7: Soft capsule
Strawberry seed oil 87.0wt%
Emulsifier 12.0
Strawberry seed extract 1.0
100.0wt%

Formulation Example 8: Tablet
Lactose 54.0wt%
Crystalline cellulose 30.0
Starch degradation product 10.0
Glycerin fatty acid ester 5.0
Strawberry seed extract 1.0
100.0wt%

Formulation Example 9: Oral granules (pharmaceuticals)
Strawberry seed extract 1.0wt%
Lactose 30.0
Cornstarch 60.0
Crystalline cellulose 8.0
Polyvinylpyrrolidone 1.0
100.0wt%

Formulation Example 10: Cat food
Corn 34.0wt%
Flour 35.0
Meat meal 15.0
Beef tallow 8.9
Salt 1.0
Skipjack extract 4.0
Strawberry seed extract 1.0
Taurine 0.1
Vitamins 0.5
Minerals 0.5
100.0wt%

Formulation Example 11: Dog food
Corn 30.0wt%
Meat (chicken) 15.0
Defatted soybean 10.0
Flour 25.0
Mosses 5.0
Strawberry seed extract 5.0
Animal fats and oils 8.9
Oligosaccharide 0.1
Vitamin 0.5
Mineral 0.5
100.0wt%
Formulation Example 12: Cosmetic cream
Squalane 20.0wt%
Beeswax 5.0
Refined jojoba oil 5.0
Glycerin 5.0
Glycerol monostearate 2.0
Polyoxyethylene (20) sorbitan-
Monostearate 2.0
Strawberry seed extract 2.0
Preservative appropriate amount
Perfume
Purified water residue
100.0wt%

Formulation Example 13: Lotion
Ethanol 5.0wt%
Glycerin 2.0
1,3-butylene glycol 2.0
Polyethylene oleyl ether 0.5
Sodium citrate 0.1
Citric acid 0.1
Strawberry seed extract 0.1
Purified water residue
100.0wt%

Formulation Example 14: Body gel
Macadamia nut oil 2.0wt%
Octyldodecyl myristate 10.0
Methylphenylpolysiloxane 5.0
Behenyl alcohol 3.0
Stearic acid 3.0
Batyl alcohol 1.0
Glyceryl monostearate 1.0
Tetraoleic acid polyoxyethylene sorbit 2.0
Hydrogenated soybean phospholipid 1.0
Ceramide 0.1
Retinol palmitate 0.1
Preservative appropriate amount
Centella extract 1.0
Strawberry seed extract 1.0
1,3-butylene glycol 5.0
Purified water residue
100.0wt%

Formulation Example 15: Latex
Squalane 4.0wt%
Vaseline 2.5
Cetanol 2.0
Glycerin 2.0
Lipophilic glyceryl monostearate 1.0
Stearic acid 1.0
L-Arginine 1.0
Strawberry seed extract 0.5
Potassium hydroxide 0.1
Perfume
Purified water residue
100.0wt%

Formulation Example 16: Bath agent (liquid)
Propylene glycol 50.0wt%
Ethanol 20.0
Sodium sulfate 5.0
Strawberry seed extract 0.5
Lanolin 0.5
Avocado oil 0.5
Dye 1.5
Fragrance 22.0
100.0wt%

  As described above, the present invention promotes gene expression of aquaporin 7, PPARγ, adiponectin, GLUT4, insulin receptor and the like, thereby improving fat metabolism and further having a function capable of preventing diabetes. Drugs, food and drinks, etc. can be provided.

It is a graph which shows the effect | action which acts on the expression of AQP7 gene in the fat of the strawberry seed extract administration mouse | mouth. It is a graph which shows the effect | action which acts on the expression of the Adipo gene in the fat of the strawberry seed extract administration mouse | mouth. It is a graph which shows the effect | action which acts on the expression of the PPAR (gamma) gene in the fat of the strawberry seed extract administration mouse | mouth. It is a graph which shows the effect | action which acts on the expression of the insulin receptor (Insr) gene in the fat of the mouse | mouth with strawberry seed extract administration. It is a graph which shows the effect | action which acts on the expression of the glucose transporter (GLUT4) gene in the fat of a strawberry seed extract administration mouse | mouth. It is a graph which shows the result of the Lpin1 gene expression effect in Example 2 and Example 3. It is a graph which shows the result of the PPAR (alpha) gene expression effect | action in Example 2 and Example 3. FIG. It is a graph which shows the result of the CPT1 gene expression effect in Example 2 and Example 3. It is a graph which shows the result of the ACOX1 gene expression effect in Example 2 and Example 3. It is a graph which shows the result of the PPARγ gene expression action in Example 2 and Example 3. It is a graph which shows the result of the Insr gene expression action in Example 2 and Example 3. It is a graph which shows the result of the GLUT4 gene expression effect in Example 2 and Example 3. It is a graph which shows the result of the Adipo gene expression effect in Example 2 and Example 3.

Claims (10)

  Fat metabolism improvement gene expression promoter comprising an extract of Rosaceae Fragaria L. as an active ingredient.   The fat metabolism-improving gene expression promoter according to claim 1, wherein the extract contains tyrilloside.   The fat metabolism-improving gene expression promoter according to claim 1 or 2, wherein seeds are used as a part of the Rosaceae fragrant genus (Rosaceae Fragaria L.).   Diabetes prevention-related gene expression promoter comprising an extract of Rosaceae Fragaria L.   5. The diabetes prevention-related gene expression promoter according to claim 4, wherein the extract contains tyrilloside.   6. The diabetes prevention-related gene expression promoter according to claim 4 or 5, wherein seeds are used as a part of the Rosaceae Fragaria L ..   A food or drink comprising the fat metabolism improving gene expression promoter according to any one of claims 1 to 6 and a diabetes prevention-related gene expression promoter.   A skin external preparation for mammals including humans, comprising the fat metabolism-improving gene expression promoter according to any one of claims 1 to 6 and a diabetes prevention-related gene expression promoter.   A pharmaceutical product for mammals including humans, comprising the fat metabolism improving gene expression promoter according to any one of claims 1 to 6 and a diabetes prevention-related gene expression promoter.   A feed for mammals comprising the fat metabolism improving gene expression promoter according to any one of claims 1 to 6 and a diabetes prevention-related gene expression promoter.