Composition

Abstract

Provision of technology for enhancing PGC-1α gene expression, etc. [Solution] A composition for enhancing PGC-1α gene expression, which contains as an active ingredient a whey protein hydrolysate having the following physicochemical properties (1) to (3): (1) The average molecular chain length of the whey protein hydrolysate is 2 to 10. (2) The fraction of whey protein hydrolysate having a molecular weight of 5,000 to 10,000 daltons accounts for 8% or less of the total whey protein hydrolysate. (3) The amount of free amino acids relative to the total amount of amino acids in the whey protein hydrolysate is 10% or less.

Description

[Technical Field]

[0001] The present invention relates to a composition, specifically to a composition for enhancing PGC-1α gene expression. [Background technology]

[0002] PGC-1α (Peroxisome proliferator-activated receptor gamma co-activator 1α) is a master regulator of the mitochondrial biogenesis pathway and is known to have a beneficial effect on mitochondrial dysfunction and insulin resistance (Non-Patent Document 1). Furthermore, it has been reported that transgenic mice in which PGC-1α is overexpressed specifically in adipose tissue are able to prevent or treat impaired glucose tolerance, adipose tissue hypertrophy, adipose tissue fibrosis, and fatty liver (Non-Patent Document 2).

[0003] PGC-1α is also associated with fatty acid β-oxidation. Enhanced expression of the PGC-1α gene promotes mitochondrial biosynthesis or treats mitochondrial dysfunction, resulting in enhanced fatty acid β-oxidation activity. Enhanced fatty acid β-oxidation promotes fat burning and energy consumption. It has been suggested that impaired fatty acid β-oxidation activity may be a cause of diseases such as insulin resistance, diabetes, obesity, renal fibrosis, and heart failure (Non-Patent Document 3).

[0004] In addition, increased energy intake due to overeating leads to an increase in white adipose tissue, which can lead to obesity and metabolic syndrome. On the other hand, brown fat is activated by eating and has been suggested to play a role in consuming excess energy through diet-induced thermogenesis. UCP-1 (uncoupling protein 1) plays an important role in thermogenesis of brown fat (Non-Patent Document 4).

[0005] Meanwhile, technologies have been developed that use whey protein hydrolysates with specific physicochemical properties as active ingredients, such as blood uric acid level-reducing agents that contain such hydrolysates as active ingredients (Patent Document 1). [Prior art documents] [Patent documents]

[0006] [Patent Document 1] Japanese Patent Application Publication No. 2019-043871 [Non-patent literature]

[0007] [Non-Patent Document 1] Jens Frey Halling et al., Appl Physiol Nutr Metab. 45, 9, 927-936 (2020) [Non-patent document 2] Shin-Hsueh Shen et al., Antioxidants (Basel). 11, 6, 1147 (2022) [Non-patent document 3] Sander M Houtenet al., Annu Rev Physiol. 78, 23-44 (2016) [Non-patent document 4] Okamatsu et al., Journal of Japanese Biochemical Society, 93, 1, 24-34 (2021) Summary of the Invention [Problem to be solved by the invention]

[0008] An objective of the present invention is to provide a technique for enhancing PGC-1α gene expression and the like. [Means for solving the problem]

[0009] The present inventors have found that the above problems can be solved by focusing on whey protein hydrolysates having specific physicochemical properties, and have completed the present invention.

[0010] The present invention provides It is possible to provide a composition for enhancing PGC-1α gene expression, which contains as an active ingredient a whey protein hydrolysate having the following physicochemical properties (1) to (3): (1) The average molecular chain length of the whey protein hydrolysate is 2 to 10. (2) The fraction of whey protein hydrolysate having a molecular weight of 5,000 to 10,000 daltons accounts for 8% or less of the total whey protein hydrolysate. (3) The amount of free amino acids relative to the total amount of amino acids in the whey protein hydrolysate is 10% or less.

[0011] The present invention also provides It is possible to provide a composition for enhancing UCP-1 gene expression, which contains as an active ingredient a whey protein hydrolysate having the following physicochemical properties (1) to (3): (1) The average molecular chain length of the whey protein hydrolysate is 2 to 10. (2) The fraction of whey protein hydrolysate having a molecular weight of 5,000 to 10,000 daltons accounts for 8% or less of the total whey protein hydrolysate. (3) The amount of free amino acids relative to the total amount of amino acids in the whey protein hydrolysate is 10% or less.

[0012] The present invention also provides It is possible to provide a composition for enhancing fatty acid β-oxidation activity, which contains as an active ingredient a whey protein hydrolysate having the following physicochemical properties (1) to (3): (1) The average molecular chain length of the whey protein hydrolysate is 2 to 10. (2) The fraction of whey protein hydrolysate having a molecular weight of 5,000 to 10,000 daltons accounts for 8% or less of the total whey protein hydrolysate. (3) The amount of free amino acids relative to the total amount of amino acids in the whey protein hydrolysate is 10% or less.

[0013] The present invention also provides It is possible to provide a composition for promoting mitochondrial biogenesis, which contains as an active ingredient a whey protein hydrolysate having the following physicochemical properties (1) to (3): (1) The average molecular chain length of the whey protein hydrolysate is 2 to 10. (2) The fraction of whey protein hydrolysate having a molecular weight of 5,000 to 10,000 daltons accounts for 8% or less of the total whey protein hydrolysate. (3) The amount of free amino acids relative to the total amount of amino acids in the whey protein hydrolysate is 10% or less.

[0014] The present invention also provides It is possible to provide a composition for promoting energy consumption, which contains as an active ingredient a whey protein hydrolysate having the following physicochemical properties (1) to (3): (1) The average molecular chain length of the whey protein hydrolysate is 2 to 10. (2) The fraction of whey protein hydrolysate having a molecular weight of 5,000 to 10,000 daltons accounts for 8% or less of the total whey protein hydrolysate. (3) The amount of free amino acids relative to the total amount of amino acids in the whey protein hydrolysate is 10% or less.

[0015] The present invention also provides The active ingredient is a whey protein hydrolysate having the following physicochemical properties (1) to (3). The present invention provides a composition for use in the prevention or treatment of one or more conditions selected from the group consisting of mitochondrial dysfunction, insulin resistance, impaired glucose tolerance, adipose tissue hypertrophy, adipose tissue fibrosis, fatty liver, dyslipidemia, hypertension, heart disease, arteriosclerosis due to hypercholesterolemia, arteriosclerosis due to dyslipidemia, diabetes, obesity, metabolic syndrome, and renal fibrosis. (1) The average molecular chain length of the whey protein hydrolysate is 2 to 10. (2) The fraction of whey protein hydrolysate having a molecular weight of 5,000 to 10,000 daltons accounts for 8% or less of the total whey protein hydrolysate. (3) The amount of free amino acids relative to the total amount of amino acids in the whey protein hydrolysate is 10% or less.

[0016] In a preferred embodiment, the composition is a food or drink composition. In a preferred embodiment, the composition is a pharmaceutical composition. [Effects of the Invention]

[0017] According to the present invention, it is possible to provide a technique for enhancing PGC-1α gene expression, etc. Furthermore, according to the present invention, it is possible to provide a composition for the above-mentioned use that can be safely ingested over a long period of time. DETAILED DESCRIPTION OF THE INVENTION

[0018] The present invention will be described in detail below. However, the present invention is not limited to the following embodiments and can be freely modified within the scope of the present invention. In this specification, percentages are expressed by mass unless otherwise specified.

[0019] As used herein, the terms "ingestion," "ingest," and "ingested" may be replaced with the terms "administration," "administered," and "administered," respectively. In this specification, "disease, symptom, condition, or disorder" may be referred to as "disease, etc."

[0020] One aspect of the present invention is The composition for enhancing PGC-1α gene expression contains, as an active ingredient, a whey protein hydrolysate having the following physicochemical properties (1) to (3): (1) The average molecular chain length of the whey protein hydrolysate is 2 to 10. (2) The fraction of whey protein hydrolysate having a molecular weight of 5,000 to 10,000 daltons accounts for 8% or less of the total whey protein hydrolysate. (3) The amount of free amino acids relative to the total amount of amino acids in the whey protein hydrolysate is 10% or less.

[0021] The composition of this embodiment may be a mixture, and its components may be homogeneous or heterogeneous. The composition of this embodiment may contain the active ingredient alone, or may contain other ingredients as long as they exert the effect of enhancing PGC-1α gene expression.

[0022] The whey protein hydrolysate in this embodiment is obtained by hydrolyzing whey protein derived from milk. Whey protein contains various components, and the hydrolysate in this embodiment is obtained by hydrolyzing these components. The hydrolysis may be performed by one or more selected from the group consisting of proteolytic enzymes, acids, alkalis, and the like. Examples of whey proteins include commercially available whey products, whey separated by known methods from milk, skim milk, etc. (e.g., whey powder, desalted whey powder, etc.), separated and purified whey protein concentrate (WPC), whey protein isolate (WPI), and any of these. A mixture of proportions may be mentioned. In this embodiment, it is preferable to use whey protein derived from cow's milk, and the whey protein is preferably whey protein concentrate (WPC). Whey proteins derived from cow's milk are generally known to contain 15-25% α-lactalbumin, 50-65% β-lactoglobulin, 5-10% bovine serum albumin, lactoferrin, etc. The same is true for whey protein concentrate (WPC) and whey protein isolate (WPI).

[0023] In this embodiment, the whey protein hydrolysate is preferably a whey protein hydrolysate hydrolyzed with a protease (hereinafter, may be referred to as "enzymatically decomposed whey protein").

[0024] Examples of methods for producing the enzymatic hydrolysate of whey protein in this embodiment include, but are not limited to, the following. Specifically, first, whey protein, which is the raw material, is dispersed and dissolved in water or warm water to prepare a whey protein solution. Although there are no limitations on the concentration of the whey protein solution, it is generally preferable to set the protein concentration in the range of about 2 to 20%, preferably 5 to 15%, from the viewpoints of efficiency and operability. A dissolution concentration of 2% or higher improves production efficiency, while a dissolution concentration of 20% or lower is desirable because it can suppress the risk of reduced decomposition efficiency, burning during heat treatment, and increased viscosity during cooling.

[0025] The pH of the whey protein solution is preferably adjusted using an acid or alkali solution so that it falls within the optimal pH range for the protease used in this embodiment. The pH of the whey protein solution is preferably adjusted to a pH of 6.5 or higher and 10.0 or lower before hydrolysis. As a treatment step before hydrolysis, a heat treatment, an ion exchange treatment, or the like may be carried out before or after the pH adjustment, or both.

[0026] A proteolytic enzyme is added to a whey protein solution whose pH has been appropriately adjusted to carry out hydrolysis. The proteolytic enzyme used in the production of the whey protein hydrolysate in this embodiment is not particularly limited, but is preferably a protease, more preferably an endoprotease, and may be used in combination with an exoprotease as needed. Note that the enzymes used in this embodiment may be a single enzyme or a combination of multiple enzymes. Examples of endoproteases used in this embodiment include commercially available products such as Bioprase (manufactured by Nagase Biochemical Industry Co., Ltd.), Protin SD-AY10 (manufactured by Amano Enzyme Inc.), Protin NY100 (manufactured by Amano Enzyme Inc.), Protease N Amano (manufactured by Amano Enzyme Inc.), Neutrase (manufactured by Novo Nordisk), Alcalase (manufactured by Novo Nordisk Inc.), trypsin (manufactured by Novo Nordisk Inc.), chymotrypsin (manufactured by Novo Nordisk Inc.), papain (manufactured by Amano Enzyme Inc.), and bromelain (manufactured by Amano Enzyme Inc.). Furthermore, examples of exoproteases used in this embodiment include commercially available products such as Protease A Amano (manufactured by Amano Enzyme Inc.), Sumizyme LP50D (manufactured by Shin-Nihon Kagaku Kogyo Co., Ltd.), and Flavorzyme (manufactured by Novo Nordisk).

[0027] The whey protein solution to which the protease has been added is preferably hydrolyzed under predetermined treatment conditions, specifically by incubating the solution for a predetermined period of time at an optimum temperature for the enzyme used. The optimum temperature is preferably 30 to 60°C, more preferably 40 to 55°C, and the treatment time is preferably 2 to 24 hours, more preferably 3 to 12 hours. The whey protein solution is preferably kept at this temperature range for a certain period of time to be hydrolyzed by the enzyme. Furthermore, the pH of the whey protein solution at this time is preferably adjusted to a pH of 6 to 11, more preferably 6.5 to 10, and even more preferably 7 to 9. The enzymes can be added simultaneously or at appropriate intervals, and immobilized enzymes can also be used. The pH of the solution can also be adjusted appropriately during hydrolysis to maintain the optimum pH for the enzyme.

[0028] When the whey protein solution is hydrolyzed by batch processing, the hydrolyzed solution is heated by a conventional method to inactivate the enzyme. The heating temperature and holding time are preferably set appropriately to ensure sufficient inactivation, taking into consideration the thermal stability of the enzyme used. After the heat treatment, the solution is cooled by a conventional method, and can be dried as is or, if necessary, concentrated to obtain a powder product.

[0029] The whey protein hydrolysate in this embodiment can be appropriately adjusted and produced by the above-mentioned methods so as to have the physicochemical properties (1) to (3) above.

[0030] The whey protein hydrolysate in this embodiment preferably has one or more physicochemical properties selected from the group consisting of the following (4) to (6): (4) The transmittance at 540 nm in a 10% by mass whey protein hydrolysate solution is 95% or more. (5) When a 5% by mass whey protein hydrolysate solution is heated at 120°C for 10 minutes at a pH of 4 to 7, no precipitation occurs. (6) A 5% by mass whey protein hydrolysate solution does not gel even when heated at 85°C for 10 minutes in the presence of 0.025 mol / L calcium chloride at a pH of 3 to 5.

[0031] The average molecular chain length of the whey protein hydrolysate is preferably 2 to 10, more preferably 3 to 5. The average molecular chain length of the whey protein hydrolysate can be measured by the TNBS method (see "3) TNBS method for measuring average peptide chain length" in "Journal of the Japanese Society of Nutrition and Food Science, Vol. 47, No. 3, pp. 195-201 (1994)").

[0032] In the whey protein hydrolysate, the fraction having a molecular weight of 5,000 to 10,000 daltons preferably accounts for 8% or less of the total whey protein hydrolysate, more preferably 5% or less, and even more preferably 2% or less. The molecular weight of the whey protein hydrolysate can be measured by the <Measurement of molecular weight distribution> described below.

[0033] <Measurement of molecular weight distribution> The molecular weight distribution is measured by high performance liquid chromatography (N. Ui et al., eds., "High Performance Liquid Chromatography of Proteins and Peptides," Chemical Special Issue No. 102, p. 241, Kagaku Dojin Co., Ltd., 1984). Specifically, a polyhydroxyethyl aspartamide column (Poly LC) with a diameter of 4.6 mm and a length of 22 mm was used. 0 mM] and eluted with 20 mM sodium chloride and 50 mM formic acid at an elution rate of 0.5 mL / min. A UV detector (Shimadzu Corporation) is used for detection, and a GPC analysis system (Shimadzu Corporation) is used for data analysis. [Percentage (%) of each molecular weight fraction] = [area of ​​each molecular weight range in the molecular weight distribution / total area (total area) of the whey protein hydrolysate in the molecular weight distribution].

[0034] The amount of free amino acids relative to the total amount of amino acids in the whey protein hydrolysate is preferably 10% or less, more preferably 8% or less, and even more preferably 6% or less. The whey protein hydrolysate has an advantage in that the amount of free amino acids relative to the total amount of amino acids is within the above range, and therefore the whey protein hydrolysate used in this embodiment has a good flavor even when ingested alone without being mixed with other foods or beverages. The amount of free amino acids contained in the whey protein hydrolysate used in this embodiment can be measured by the formula: Percentage of total mass of free amino acids (%) = (mass of total free amino acids / mass of total amino acids) × 100 (see <Method for calculating free amino acid rate> described in JP 2017-31105 A).

[0035] The whey protein hydrolysate used in this embodiment preferably has a transmittance of 95% or more, more preferably 97% or more, at 540 nm in a 10% by mass solution of the whey protein hydrolysate, which is prepared by dissolving powdered whey protein hydrolysate in water to form a 10% by mass (mass / volume) aqueous solution. When the transmittance at 540 nm of the 10% by mass whey protein hydrolysate solution is within the above range, the solution is transparent, which is advantageous in that it can be applied to a wide range of products such as foods and pharmaceuticals.

[0036] The whey protein hydrolysate used in this embodiment preferably does not produce precipitation when a 5% by mass whey protein hydrolysate solution (adjusted to a pH of 4 to 7) is heat-treated at 120°C for 10 minutes. Furthermore, it is preferable that the whey protein hydrolysate used in this embodiment does not gel even when it is heated at 85°C for 10 minutes after adding calcium chloride to make the concentration 0.025 mol / L, adjusting the pH to 3 to 5, and making it into a 5% by mass aqueous solution. The 5% by mass whey protein hydrolysate solution was prepared by preparing a 5% by mass (mass / volume) aqueous solution of powdered whey protein hydrolysate.

[0037] Furthermore, the whey protein hydrolysate in this embodiment is highly soluble in water, and therefore has excellent processing stability, a less bitter taste, and a good flavor. Furthermore, whey protein is empirically known to be highly safe, and therefore can be safely and continuously ingested for a long period of time.

[0038] As shown in the Examples below, the whey protein hydrolysate of this embodiment has the effect of enhancing the expression of the PGC-1α gene, and therefore can be used to enhance the expression of the PGC-1α gene. Furthermore, since enhanced expression of the PGC-1α gene promotes mitochondrial biosynthesis, the whey protein hydrolysate in this embodiment can be used to promote mitochondrial biosynthesis. Furthermore, since the whey protein hydrolysate in this embodiment can be used to enhance the expression of the PGC-1α gene, it can be used to prevent or treat diseases that can be prevented or treated by enhancing the expression of the PGC-1α gene. It can also be used to prevent or treat diseases that can be prevented or treated by promoting mitochondrial biosynthesis. In either case, such diseases include, for example, mitochondrial dysfunction, insulin resistance, impaired glucose tolerance, adipose tissue hypertrophy, adipose tissue fibrosis, fatty liver, dyslipidemia, hypertension, Examples of such diseases include heart disease (for example, heart failure), arteriosclerosis due to hypercholesterolemia, arteriosclerosis due to dyslipidemia, diabetes, obesity, metabolic syndrome, renal fibrosis, etc. These diseases may be high-fat diet-induced.

[0039] PGC-1α is also associated with fatty acid β-oxidation. Enhanced expression of the PGC-1α gene promotes mitochondrial biogenesis or treats mitochondrial dysfunction, thereby enhancing fatty acid β-oxidation activity. Therefore, the whey protein hydrolysate of this embodiment can be used to enhance fatty acid β-oxidation activity. Furthermore, since the enhancement of fatty acid β-oxidation activity promotes fat burning and energy consumption, the whey protein hydrolysate in this embodiment can be used to promote fat burning and energy consumption. Furthermore, since the whey protein hydrolysate in this embodiment can be used to enhance fatty acid β-oxidation activity, it can be used for diseases that can be prevented or treated by enhancing fatty acid β-oxidation activity. It can also be used for diseases that can be prevented or treated by promoting energy consumption. In either case, examples of such diseases include mitochondrial dysfunction, insulin resistance, impaired glucose tolerance, adipose tissue hypertrophy, adipose tissue fibrosis, fatty liver, dyslipidemia, hypertension, heart disease (e.g., heart failure), arteriosclerosis due to hypercholesterolemia, arteriosclerosis due to dyslipidemia, diabetes, obesity, metabolic syndrome, and renal fibrosis. These diseases may be high-fat diet-induced.

[0040] The composition of this embodiment may be used for non-therapeutic purposes or for therapeutic purposes. "Non-therapeutic purposes" are purposes that do not include medical procedures. In other words, purposes that do not include treatment of a subject through therapy. Examples include uses for maintaining or promoting health.

[0041] When the composition of this embodiment is used for non-therapeutic purposes, it can be administered to healthy individuals. A "healthy individual" may be a person who, at the time of taking the composition of this embodiment, does not have a disease that can be prevented or treated by enhancing the expression of the PGC-1α gene, a person who is concerned about a disease that can be prevented or treated by enhancing the expression of the PGC-1α gene, or a person who is at risk of a disease that can be prevented or treated by enhancing the expression of the PGC-1α gene. When the composition of this embodiment is used for non-therapeutic purposes, it becomes possible to prevent diseases in healthy individuals that can be prevented or treated by enhancing the expression of the PGC-1α gene.

[0042] When the composition of this embodiment is used for therapeutic purposes, the subject can be a non-healthy individual. The "unhealthy individual" may be a person who, at the time of taking the composition of this embodiment, suffers from a disease that can be prevented or treated by enhancing the expression of the PGC-1α gene. When the composition of this embodiment is used for therapeutic purposes, it becomes possible to treat diseases that can be prevented or treated by enhancing the expression of the PGC-1α gene in unhealthy individuals.

[0043] The content of the whey protein hydrolysate in the composition of this embodiment is appropriately set depending on the embodiment of the composition, and is, for example, 5% or more, 10% or more, 20% or more, or 90% or less, 80% or less, 70% or less, etc., or any compatible combination thereof, such as 5 to 90%, 10 to 80%, 20 to 70%, etc.

[0044] The proportion of the whey protein hydrolysate in the composition of this embodiment may be determined depending on the amount of the composition that a consumer ingests per serving and the amount of the whey protein hydrolysate to be contained in the composition of this embodiment.

[0045] The intake amount (effective amount) of the composition of this embodiment is appropriately determined depending on the form of the composition, the method of use, the subject, the age and sex of the subject, and other conditions, but is not particularly limited as long as the effect of enhancing the expression of the PGC-1α gene or subsequent effects is exhibited in the subject who ingested it. The amount of whey protein hydrolysate is, for example, 2 g / day or more, 5 g / day or more, or 50 g / day or less, 20 g / day or less, etc. A consistent combination thereof is also acceptable, for example, 2 to 50 g / day, 2 to 20 g / day, 5 to 20 g / day, etc. The amount per 1 kg of body weight is, for example, 0.01 g / kg body weight / day or more, 0.05 g / kg body weight / day or more, or 1 g / kg body weight / day or less, 0.5 g / kg body weight / day or less, etc. Consistent combinations of these are also acceptable, such as 0.01 to 1 g / kg body weight / day, 0.05 to 0.5 g / kg body weight / day, etc.

[0046] The number of times the composition of this embodiment is ingested per day is not particularly limited, and can be determined appropriately depending on the amount of the whey protein hydrolysate ingested per day. The composition of this embodiment is preferably taken regularly for a certain period of time, preferably 6 weeks or more, more preferably 12 weeks or more, and even more preferably 18 weeks or more.

[0047] The composition of this embodiment can be taken orally, but is not limited to this, and may also be taken nasally, or via a gastrostomy or enterostomy. For example, it may be administered to a subject via a nasogastric tube or the like.

[0048] The composition of this embodiment can be used, for example, as a food or drink composition or a pharmaceutical composition. For example, the whey protein hydrolysate can be provided as a food or beverage composition for enhancing PGC-1α gene expression, which contains the whey protein hydrolysate as an active ingredient. Hereinafter, this may be referred to as "the food or beverage composition of this embodiment." Alternatively, the whey protein hydrolysate can be provided as a pharmaceutical composition for enhancing PGC-1α gene expression, which contains the whey protein hydrolysate as an active ingredient. Hereinafter, this may be referred to as "the pharmaceutical composition of this embodiment."

[0049] The food and drink composition of this embodiment is not particularly limited as long as it contains the whey protein hydrolysate. The food and drink composition may be in any form, such as liquid, paste, gel-like solid, or powder, and may include, in addition to tablet confectionery and liquid food, wheat flour products such as bread, macaroni, spaghetti, noodles, cake mix, fried chicken flour, and breadcrumbs; instant noodles, cup noodles, retort-packed and cooked foods, canned foods, microwave-safe foods, instant soups and stews, instant miso soups and clear soups, canned soups, freeze-dried foods, and other instant foods; canned agricultural products, canned fruits, etc. processed agricultural products such as jams and marmalades, pickles, boiled beans, dried agricultural goods, and cereals (processed grain products); processed seafood products such as canned seafood, fish ham and sausage, fish paste products, seafood delicacies, and tsukudani (simmered fish dishes); processed livestock products such as canned livestock paste, livestock ham and sausage; processed milk, milk drinks, yogurt, lactic acid bacteria drinks, cheese, ice cream, infant formula, cream, and other dairy products; fats and oils such as butter, margarines, and vegetable oils; soy sauce, miso, sausage Basic seasonings such as seasonings, processed tomato seasonings, mirin, vinegars, etc.; complex seasonings and foods such as cooking mixes, curry bases, sauces, dressings, noodle soups, spices, and other complex seasonings; frozen foods such as frozen ingredients, semi-cooked frozen foods, and cooked frozen foods; confectioneries such as caramel, candy, gummies, chewing gum, chocolate, cookies, biscuits, cakes, pies, snacks, crackers, Japanese sweets, rice snacks, bean snacks, dessert sweets, jellies, and other sweets. Subcategories include carbonated drinks, natural fruit juices, fruit juice drinks, soft drinks with fruit juice, fruit pulp drinks, fruit drinks with fruit pieces, vegetable drinks, soy milk, soy milk drinks, coffee drinks, tea drinks, powdered drinks, concentrated drinks, sports drinks, nutritional drinks, alcoholic drinks, and other beverages, as well as other commercially available foods such as baby food, furikake, and ochazuke nori seaweed; infant formula; enteral nutritional foods; special purpose foods, health functional foods (foods for specified health uses, foods with nutrient functions, foods with functional claims); and nutritional supplements. The food and drink composition of this embodiment may be a supplement, for example, a tablet-shaped supplement. When it is a supplement, the whey protein hydrolyzate can be consumed without being affected by other foods in terms of the daily dietary amount and calorie intake. Can be obtained.

[0050] The food and beverage composition of this embodiment can be produced by adding the whey protein hydrolysate to the raw materials of a normal food or beverage, and can be produced in the same manner as normal food and beverages except for the addition of the whey protein hydrolysate. The addition of the whey protein hydrolysate may be carried out at any stage in the production process of the food and beverage composition.

[0051] The food and drink composition of this embodiment also includes raw materials for producing the food and drink composition, and food additives and the like that are added to the food and drink composition during or after the production of the food and drink composition.

[0052] Furthermore, the food and beverage composition of this embodiment can contain known or future components with prebiotic effects or components that supplement the prebiotic effects (hereinafter referred to as "prebiotics"), as long as they do not impair the effects of this embodiment. For example, the food and beverage composition of this embodiment can be produced by blending the whey protein hydrolysate with prebiotics such as various proteins such as whey protein, casein protein, soy protein, or pea protein, or mixtures or hydrolysates thereof; amino acids such as leucine, valine, isoleucine, or glutamine; vitamins such as vitamin B6 or vitamin C; creatine; citric acid; fish oil; or oligosaccharides such as isomaltooligosaccharides, xylooligosaccharides, soybean oligosaccharides, fructooligosaccharides, and lactulose.

[0053] The content of whey protein hydrolysate in the food and beverage composition of this embodiment is appropriately set depending on the embodiment of the food and beverage composition, but is, for example, 5% or more, 10% or more, 20% or more, or 90% or less, 80% or less, 70% or less, etc. Consistent combinations thereof are also acceptable, for example, 5 to 90%, 10 to 80%, 20 to 70%, etc.

[0054] The proportion of the whey protein hydrolysate in the food and beverage composition of this embodiment may be determined depending on the amount of the food and beverage composition ingested by a consumer per serving and the amount of the whey protein hydrolysate to be contained in the food and beverage composition of this embodiment.

[0055] The intake amount (effective amount) of the food and beverage composition of this embodiment is appropriately determined depending on the form of the food and beverage composition, the method of use, the subject, the subject's age, sex, and other conditions, but is not particularly limited as long as the effect of enhancing PGC-1α gene expression or subsequent effects is exhibited in the subject who ingests it, and the amount of the whey protein hydrolysate is, for example, 2 g / day or more, 5 g / day or more, or 50 g / day or less, 20 g / day or less, etc. Consistent combinations thereof are also acceptable, such as 2 to 50 g / day, 2 to 20 g / day, 5 to 20 g / day, etc. The amount per 1 kg of body weight is, for example, 0.01 g / kg body weight / day or more, 0.05 g / kg body weight / day or more, or 1 g / kg body weight / day or less, 0.5 g / kg body weight / day or less, etc. Consistent combinations of these are also acceptable, such as 0.01 to 1 g / kg body weight / day, 0.05 to 0.5 g / kg body weight / day, etc.

[0056] The number of times the food and drink composition of this embodiment is ingested per day is not particularly limited, and can be determined appropriately depending on the amount of the whey protein hydrolysate ingested per day. The food and drink composition of this embodiment is preferably taken regularly for a certain period of time, preferably 6 weeks or more, more preferably 12 weeks or more, and even more preferably 18 weeks or more.

[0057] The food and drink composition of this embodiment may be ingested alone or together with other food and drink compositions, foods and drinks, pharmaceutical compositions, or medicines. It may be taken together with other food and drink compositions or foods and drinks for enhancing PGC-1α gene expression, or pharmaceutical compositions or medicines for enhancing PGC-1α gene expression.

[0058] The food and drink composition of this embodiment can be sold as a food and drink composition or food and drink labeled with the use of enhancing PGC-1α gene expression, etc. Needless to say, any other wording may be used as long as it expresses the effect secondary to the use.

[0059] The above-mentioned "indication" means all acts for informing consumers of the above-mentioned uses, and any indication that can recall or infer the above-mentioned uses falls under the "indication" of the present invention, regardless of the purpose of the indication, the content of the indication, the object or medium on which it is displayed, etc. However, it is preferable to display the use in an expression that allows consumers to directly recognize the above-mentioned uses. Specifically, examples include the act of describing the above use on the food and beverage composition or food and beverage product or product packaging of this embodiment, the act of transferring, delivering, displaying for transfer or delivery, or importing the product or product packaging on which the above use is described, the act of describing the above use in advertisements, price lists, or transaction documents for the product and displaying or distributing them, or the act of describing the above use in information containing these contents and providing it by electromagnetic means (such as the Internet), and particularly displaying on promotional materials at sales sites such as packaging, containers, catalogs, pamphlets, POP, and other documents, etc.

[0060] Furthermore, the labeling is preferably one approved by the government or the like (e.g., labeling approved under various government systems and made in a manner based on such approval). Examples include labeling as a health food, more specifically, a health food, a functional food, an enteral nutritional food, a food for special dietary uses, a food with nutrient functions, a quasi-drug, etc. Other examples include labeling approved by the Consumer Affairs Agency, such as a food for specified health uses, a food with nutrient functions, a food with functional claims, and labeling approved under similar systems. Examples of the latter include labeling as a food for specified health uses, a labeling as a conditional food for specified health uses, a labeling claiming to affect the structure or function of the body, a labeling claiming to reduce disease risk, and a labeling claiming functionality based on scientific evidence. More specifically, examples include labeling as a food for specified health uses (especially a labeling claiming health uses) as defined in the Cabinet Office Ordinance on the Permission for Labeling for Special Dietary Uses Provided in the Health Promotion Act (Cabinet Office Ordinance No. 57 of August 31, 2009), and similar labeling.

[0061] Examples of such indications include "For those concerned about body fat," "For those who are slightly obese," "For those concerned about weight (BMI)," "Reduces high BMI," and "Helps improve high BMI." Examples of claims include "lose weight," "lose belly fat," "lose weight and belly fat," "lose waist circumference," and "makes fat consumption easier."

[0062] The food and beverage composition of this embodiment can be used for any subject, including healthy and unhealthy individuals, but when it is made into a food or beverage with a specific use or function indicated, it is used for the above-mentioned non-therapeutic purposes.

[0063] The pharmaceutical composition of this embodiment is not particularly limited as long as it contains the whey protein hydrolysate. As the pharmaceutical composition of this embodiment, the whey protein hydrolysate may be used as is, or may be formulated by blending it with a physiologically acceptable liquid or solid pharmaceutical carrier.

[0064] The dosage form of the pharmaceutical composition of this embodiment is not particularly limited, and specific examples include tablets, pills, powders, liquids, suspensions, emulsions, granules, capsules, syrups, suppositories, injections, ointments, patches, eye drops, and nasal drops. In addition, when formulating the pharmaceutical composition, excipients, binders, disintegrants, lubricants, stabilizers, flavorings, diluents, surfactants, or the like that are commonly used as pharmaceutical carriers may be used. Additives such as injectable solvents can be used.

[0065] As the pharmaceutical carrier, various organic or inorganic carriers can be used depending on the dosage form. Examples of carriers for solid preparations include excipients, binders, disintegrants, lubricants, stabilizers, and flavoring agents.

[0066] Examples of excipients include sugar derivatives such as lactose, sucrose, glucose, mannitol, and sorbitol; starch derivatives such as corn starch, potato starch, α-starch, dextrin, and carboxymethyl starch; cellulose derivatives such as crystalline cellulose, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, carboxymethyl cellulose, and carboxymethyl cellulose calcium; gum arabic; dextran; pullulan; silicate derivatives such as light anhydrous silicic acid, synthetic aluminum silicate, and magnesium aluminometasilicate; phosphate derivatives such as calcium phosphate; carbonate derivatives such as calcium carbonate; and sulfate derivatives such as calcium sulfate.

[0067] Examples of binders include gelatin, polyvinylpyrrolidone, macrogol, and the like, in addition to the above-mentioned excipients.

[0068] Examples of disintegrants include the above-mentioned excipients as well as chemically modified starch or cellulose derivatives such as croscarmellose sodium, carboxymethyl starch sodium, and cross-linked polyvinylpyrrolidone.

[0069] Examples of lubricants include talc; stearic acid; metal stearates such as calcium stearate and magnesium stearate; colloidal silica; veegum; waxes such as gaelt; boric acid; glycol; carboxylic acids such as fumaric acid and adipic acid; sodium carboxylates such as sodium benzoate; sulfates such as sodium sulfate; leucine; lauryl sulfates such as sodium lauryl sulfate and magnesium lauryl sulfate; silicic acids such as silicic anhydride and silicic acid hydrate; and starch derivatives.

[0070] Examples of stabilizers include paraoxybenzoic acid esters such as methylparaben and propylparaben; alcohols such as chlorobutanol, benzyl alcohol and phenylethyl alcohol; benzalkonium chloride; acetic anhydride; sorbic acid; and the like.

[0071] Examples of flavoring agents include sweeteners, acidulants, and fragrances. In the case of a liquid preparation for oral administration, examples of the carrier to be used include a solvent such as water, a flavoring agent, and the like.

[0072] The content of the whey protein hydrolysate in the pharmaceutical composition of this embodiment is appropriately determined depending on the embodiment of the pharmaceutical composition, and may be, for example, 5% or more, 10% or more, 20% or more, or 90% or less, 80% or less, 70% or less, etc., or any compatible combination thereof, such as 5 to 90%, 10 to 80%, 20 to 70%, etc.

[0073] The proportion of the whey protein hydrolysate in the pharmaceutical composition of this embodiment may be determined depending on the amount of the pharmaceutical composition to be administered to a recipient per dose and the amount of the whey protein hydrolysate to be contained in the pharmaceutical composition of this embodiment.

[0074] The dosage (effective amount) of the pharmaceutical composition of this embodiment is appropriately determined depending on the form of the pharmaceutical composition, the method of use, the subject, the age and sex of the subject, and other conditions, and is not particularly limited as long as the effect of enhancing the expression of the PGC-1α gene or subsequent effects is exhibited in the subject to which it is administered. For example, the amount of the whey protein hydrolysate is 2 g / day or more, 5 g / day or more. On the other hand, it may be 50g / day or less, 20g / day or less, etc., or any combination thereof that does not contradict each other, such as 2-50g / day, 2-20g / day, 5-20g / day, etc. The amount per 1 kg of body weight is, for example, 0.01 g / kg body weight / day or more, 0.05 g / kg body weight / day or more, or 1 g / kg body weight / day or less, 0.5 g / kg body weight / day or less, etc. Consistent combinations of these are also acceptable, such as 0.01 to 1 g / kg body weight / day, 0.05 to 0.5 g / kg body weight / day, etc.

[0075] The pharmaceutical composition of this embodiment may be administered to a non-healthy subject for the therapeutic purpose of treating a disease or the like that can be prevented or treated by enhancing the expression of the PGC-1α gene. Furthermore, the pharmaceutical composition of this embodiment may be administered to healthy subjects for the non-therapeutic purpose of preventing diseases that can be prevented or treated by enhancing the expression of the PGC-1α gene.

[0076] The pharmaceutical composition of this embodiment may be administered alone or together with another pharmaceutical composition or drug, or a food or drink composition or food or drink, for example, together with another pharmaceutical composition or drug for enhancing PGC-1α gene expression, or a food or drink composition or food or drink, etc. for enhancing PGC-1α gene expression.

[0077] Another aspect of the present invention is The composition for enhancing UCP-1 gene expression contains, as an active ingredient, a whey protein hydrolysate having the following physicochemical properties (1) to (3): (1) The average molecular chain length of the whey protein hydrolysate is 2 to 10. (2) The fraction of whey protein hydrolysate having a molecular weight of 5,000 to 10,000 daltons accounts for 8% or less of the total whey protein hydrolysate. (3) The amount of free amino acids relative to the total amount of amino acids in the whey protein hydrolysate is 10% or less.

[0078] The details of this embodiment are the same as those of the "Composition for enhancing PGC-1α gene expression" above, except as follows, and therefore, the description is incorporated herein by reference.

[0079] As shown in the Examples below, the whey protein hydrolysate of this embodiment has the effect of enhancing the expression of the UCP-1 gene, and therefore can be used to enhance the expression of the UCP-1 gene. Furthermore, since energy consumption is promoted by enhancing the expression of the UCP-1 gene, the whey protein hydrolysate in this embodiment can be used to promote energy consumption. Furthermore, since the whey protein hydrolysate in this embodiment can be used to enhance UCP-1 gene expression, it can be used to prevent or treat diseases that can be prevented or treated by enhancing UCP-1 gene expression. It can also be used to prevent or treat diseases that can be prevented or treated by promoting energy consumption. In either case, examples of the diseases include mitochondrial dysfunction, insulin resistance, impaired glucose tolerance, adipose tissue hypertrophy, adipose tissue fibrosis, fatty liver, dyslipidemia, hypertension, heart disease (e.g., heart failure), arteriosclerosis due to hypercholesterolemia, arteriosclerosis due to dyslipidemia, diabetes, obesity, metabolic syndrome, and renal fibrosis. These diseases may be high-fat diet-induced.

[0080] In this embodiment, the indication may be, for example, "For those concerned about body fat," "For those who are slightly obese," "For those concerned about weight (BMI)," "Reduces high BMI," or "For those with high BMI." "Helps improve", "lose weight", "lose belly fat", "lose weight and belly fat" Examples of claims include "reduces weight," "reduces waist circumference," and "facilitates fat burning."

[0081] As described above, the whey protein hydrolysate having the physicochemical properties (1) to (3) above can be used as an active ingredient for preventing or treating one or more conditions selected from the group consisting of mitochondrial dysfunction, insulin resistance, impaired glucose tolerance, adipose tissue hypertrophy, adipose tissue fibrosis, fatty liver, dyslipidemia, hypertension, heart disease (e.g., heart failure, etc.), arteriosclerosis due to hypercholesterolemia, arteriosclerosis due to dyslipidemia, diabetes, obesity, metabolic syndrome, and renal fibrosis (which may be high-fat diet-induced).

[0082] Therefore, the present invention provides It is also possible to provide a composition for use in the prevention or treatment of one or more conditions selected from the group consisting of mitochondrial dysfunction, insulin resistance, impaired glucose tolerance, adipose tissue hypertrophy, adipose tissue fibrosis, fatty liver, dyslipidemia, hypertension, heart disease (e.g., heart failure), arteriosclerosis due to hypercholesterolemia, arteriosclerosis due to dyslipidemia, diabetes, obesity, metabolic syndrome, and renal fibrosis (which may be high-fat diet-induced), comprising as an active ingredient a whey protein hydrolysate having the physicochemical properties (1) to (3) below. (1) The average molecular chain length of the whey protein hydrolysate is 2 to 10. (2) The fraction of whey protein hydrolysate having a molecular weight of 5,000 to 10,000 daltons accounts for 8% or less of the total whey protein hydrolysate. (3) The amount of free amino acids relative to the total amount of amino acids in the whey protein hydrolysate is 10% or less.

[0083] The details of this embodiment are the same as those explained above in relation to the "Composition for enhancing PGC-1α gene expression," and therefore, the explanation is incorporated herein by reference.

[0084] The present invention can also provide the following aspects: In the following, "a whey protein hydrolysate having the physicochemical properties (1) to (3) above" will be referred to as "the active ingredient."

[0085] Use of the active ingredient for producing a composition for enhancing PGC-1α gene expression. The active ingredient is for use in the prevention or treatment of diseases that can be prevented or treated by enhancing PGC-1α gene expression. A composition comprising the active ingredient for use in the prevention or treatment of diseases that can be prevented or treated by enhancing PGC-1α gene expression. A non-therapeutic use of the active ingredient, in which the active ingredient is used for the prevention of diseases that can be prevented by enhancing PGC-1α gene expression. A non-therapeutic use of a composition containing the active ingredient, wherein the composition is used for the prevention of diseases that can be prevented by enhancing PGC-1α gene expression. A method for preventing or treating diseases that can be prevented or treated by enhancing PGC-1α gene expression, comprising administering a prophylactically effective or therapeutically effective amount of the active ingredient to a subject in need of prevention or treatment. A method for preventing or treating diseases that can be prevented or treated by enhancing PGC-1α gene expression, comprising administering a prophylactically effective or therapeutically effective amount of a composition containing the active ingredient to a subject in need of prevention or treatment.

[0086] Use of the active ingredient for producing a composition for enhancing UCP-1 gene expression. The active ingredient is for use in the prevention or treatment of diseases that can be prevented or treated by enhancing UCP-1 gene expression. A composition comprising the active ingredient for use in the prevention or treatment of diseases that can be prevented or treated by enhancing UCP-1 gene expression. A non-therapeutic use of the active ingredient, in which the active ingredient is used for the prevention of diseases that can be prevented by enhancing UCP-1 gene expression. A non-therapeutic use of a composition containing the active ingredient, wherein the composition is used for the prevention of a disease or the like that can be prevented by enhancing UCP-1 gene expression. A method for preventing or treating a disease that can be prevented or treated by enhancing UCP-1 gene expression, comprising administering a prophylactically effective amount or a therapeutically effective amount of the active ingredient to a subject in need of prevention or treatment. A method for preventing or treating a disease that can be prevented or treated by enhancing UCP-1 gene expression, comprising administering a prophylactically effective amount or a therapeutically effective amount of a composition containing the active ingredient to a subject in need of prevention or treatment.

[0087] Use of the active ingredient for producing a composition for enhancing fatty acid β-oxidation activity. The active ingredient is for use in the prevention or treatment of diseases that can be prevented or treated by enhancing fatty acid β-oxidation activity. A composition containing the active ingredient for use in the prevention or treatment of diseases that can be prevented or treated by enhancing fatty acid β-oxidation activity. A non-therapeutic use of the active ingredient, in which the active ingredient is used for preventing diseases that can be prevented by enhancing fatty acid β-oxidation activity. A non-therapeutic use of a composition containing the active ingredient, in which the composition is used for the prevention of diseases that can be prevented by enhancing the β-oxidation activity of fatty acids. A method for preventing or treating a disease that can be prevented or treated by enhancing fatty acid beta-oxidation activity, comprising administering a prophylactically effective amount or a therapeutically effective amount of the active ingredient to a subject in need of prevention or treatment. A method for preventing or treating a disease that can be prevented or treated by enhancing fatty acid beta-oxidation activity, comprising administering a prophylactically effective amount or a therapeutically effective amount of a composition containing the active ingredient to a subject in need of prevention or treatment.

[0088] Use of the active ingredient for producing a composition for promoting mitochondrial biogenesis. The active ingredient for use in the prevention or treatment of diseases that can be prevented or treated by promoting mitochondrial biogenesis. A composition comprising the active ingredient for use in the prevention or treatment of diseases that can be prevented or treated by promoting mitochondrial biogenesis. A non-therapeutic use of the active ingredient, in which the active ingredient is used for the prevention of diseases that can be prevented by promoting mitochondrial biogenesis. A non-therapeutic use of a composition containing the active ingredient, wherein the composition is used for the prevention of diseases that can be prevented by promoting mitochondrial biogenesis. A method for preventing or treating a disease that can be prevented or treated by promoting mitochondrial biogenesis, comprising administering a prophylactically effective amount or a therapeutically effective amount of the active ingredient to a subject in need of prevention or treatment. A method for preventing or treating a disease that can be prevented or treated by promoting mitochondrial biogenesis, comprising administering a prophylactically effective amount or a therapeutically effective amount of a composition containing the active ingredient to a subject in need of prevention or treatment.

[0089] Use of the active ingredient for producing a composition for promoting energy consumption. The active ingredient for use in the prevention or treatment of diseases that can be prevented or treated by promoting energy consumption. A composition containing the active ingredient for use in the prevention or treatment of diseases that can be prevented or treated by promoting energy consumption. A non-therapeutic use of the active ingredient, in which the active ingredient is used for the prevention of diseases that can be prevented by promoting energy consumption. A non-therapeutic use of a composition containing the active ingredient, wherein the composition is used for the prevention of diseases that can be prevented by promoting energy consumption. A method for preventing or treating a disease that can be prevented or treated by promoting energy consumption, comprising administering a prophylactically effective amount or a therapeutically effective amount of the active ingredient to a subject in need of prevention or treatment. A method for preventing or treating a disease that can be prevented or treated by promoting energy consumption, comprising administering a prophylactically effective amount or a therapeutically effective amount of a composition containing the active ingredient to a subject in need of prevention or treatment.

[0090] Use of the active ingredient for manufacturing a composition used in the prevention or treatment of one or more conditions selected from the group consisting of mitochondrial dysfunction, insulin resistance, impaired glucose tolerance, adipose tissue hypertrophy, adipose tissue fibrosis, fatty liver, dyslipidemia, hypertension, heart disease (e.g., heart failure, etc.), arteriosclerosis due to hypercholesterolemia, arteriosclerosis due to dyslipidemia, diabetes, obesity, metabolic syndrome, and renal fibrosis (which may be high-fat diet-induced). The active ingredient for use in the prevention or treatment of one or more selected from the group consisting of mitochondrial dysfunction, insulin resistance, impaired glucose tolerance, adipose tissue hypertrophy, adipose tissue fibrosis, fatty liver, dyslipidemia, hypertension, heart disease (e.g., heart failure, etc.), arteriosclerosis due to hypercholesterolemia, arteriosclerosis due to dyslipidemia, diabetes, obesity, metabolic syndrome, and renal fibrosis (which may be high-fat diet-induced). A composition containing the active ingredient for use in the prevention or treatment of one or more conditions selected from the group consisting of mitochondrial dysfunction, insulin resistance, impaired glucose tolerance, adipose tissue hypertrophy, adipose tissue fibrosis, fatty liver, dyslipidemia, hypertension, heart disease (e.g., heart failure, etc.), arteriosclerosis due to hypercholesterolemia, arteriosclerosis due to dyslipidemia, diabetes, obesity, metabolic syndrome, and renal fibrosis (which may be high-fat diet-induced). Non-therapeutic use of the active ingredient, wherein the active ingredient is used for the prevention of one or more selected from the group consisting of mitochondrial dysfunction, insulin resistance, impaired glucose tolerance, adipose tissue hypertrophy, adipose tissue fibrosis, fatty liver, dyslipidemia, hypertension, heart disease (e.g., heart failure, etc.), arteriosclerosis due to hypercholesterolemia, arteriosclerosis due to dyslipidemia, diabetes, obesity, metabolic syndrome, and renal fibrosis (which may be high-fat diet-induced). Non-therapeutic use of a composition containing the active ingredient, wherein the composition is used for the prevention of one or more conditions selected from the group consisting of mitochondrial dysfunction, insulin resistance, impaired glucose tolerance, adipose tissue hypertrophy, adipose tissue fibrosis, fatty liver, dyslipidemia, hypertension, heart disease (e.g., heart failure, etc.), arteriosclerosis due to hypercholesterolemia, arteriosclerosis due to dyslipidemia, diabetes, obesity, metabolic syndrome, and renal fibrosis (which may be high-fat diet-induced). A method for preventing or treating one or more conditions selected from the group consisting of mitochondrial dysfunction, insulin resistance, impaired glucose tolerance, adipose tissue hypertrophy, adipose tissue fibrosis, fatty liver, dyslipidemia, hypertension, heart disease (e.g., heart failure, etc.), arteriosclerosis due to hypercholesterolemia, arteriosclerosis due to dyslipidemia, diabetes, obesity, metabolic syndrome, and renal fibrosis (which may be high-fat diet-induced), comprising administering a prophylactically effective amount or a therapeutically effective amount of the active ingredient to a subject in need of prevention or treatment. A method for preventing or treating one or more conditions selected from the group consisting of mitochondrial dysfunction, insulin resistance, impaired glucose tolerance, adipose tissue hypertrophy, adipose tissue fibrosis, fatty liver, dyslipidemia, hypertension, heart disease (e.g., heart failure, etc.), arteriosclerosis due to hypercholesterolemia, arteriosclerosis due to dyslipidemia, diabetes, obesity, metabolic syndrome, and renal fibrosis (which may be high-fat diet-induced), comprising administering a prophylactically effective amount or a therapeutically effective amount of a composition containing the active ingredient to a subject in need of such prevention or treatment. method. [Example]

[0091] The present invention will be explained in more detail below using examples, but the present invention is not limited to these examples.

[0092] (Preparation of test samples) A whey aqueous solution was prepared by dissolving a commercially available whey protein concentrate (Milei 80, manufactured by Mirai Co., Ltd.) in water at a concentration of 10% and adjusting the pH of the solution to 8.0 with sodium hydroxide. To this whey aqueous solution, 5,000 units of Protease N Amano (manufactured by Amano Enzyme Co., Ltd.) were added per gram of protein, and the mixture was hydrolyzed at 50°C for 7 hours at pH 8.0. The enzyme was then inactivated by heating at 90°C for 10 minutes, and the mixture was powdered using a spray dryer to obtain a dried whey protein hydrolysate.

[0093] In this study, Milei 80 (manufactured by Mirai Co., Ltd.) was used as the WPC. Generally, WPC (whey protein concentrate) contains 15-25% α-lactalbumin, 50-65% β-lactoglobulin, 5-10% bovine serum albumin, lactoferrin, etc.

[0094] The dried whey protein hydrolysate thus prepared was suspended in milliQ water to a concentration of 100 mg / mL, subjected to ultrasonic treatment for 10 minutes, and then filtered. The resulting solution was used as a test sample.

[0095] The physicochemical properties of the obtained whey protein hydrolysate were as follows: 1) The average molecular chain length of the whey protein hydrolysate was 3 to 5. The average molecular chain length was measured using the TNBS method (see "3) Average Peptide Chain Length Measurement Method, TNBS Method" in "Journal of the Japanese Society of Nutrition and Food Science, Vol. 47, No. 3, pp. 195-201 (1994)"). 2) The fraction of whey protein hydrolysate with a molecular weight of 5,000 to 10,000 daltons accounted for 2% or less of the total whey protein hydrolysate. The proportion of the fraction was measured by the method described above in <Measurement of molecular weight distribution>. 3) The amount of free amino acids relative to the total amount of amino acids in the whey protein hydrolysate was 6% or less. The amount of free amino acids contained in the whey protein hydrolysate was measured by the formula: percentage of the total mass of free amino acids (%) = (mass of total free amino acids / mass of total amino acids) × 100 (see the "Method for calculating the free amino acid ratio" described in JP 2017-31105 A). 4) The transmittance of a 10% by mass whey protein hydrolysate solution was measured using a spectrophotometer (U-2000, manufactured by Hitachi, Ltd.: 540 nm), and the transmittance of the 10% by mass whey protein hydrolysate solution at 540 nm was 97% or higher. 5) When a 5% by mass whey protein hydrolysate solution (pH 4 to 7) was heat-treated at 120°C for 10 minutes, the presence or absence of precipitation was visually confirmed, but no precipitation was observed. 6) When a 5% by mass whey protein hydrolysate solution was heat-treated at 85°C for 10 minutes in the presence of 0.025 mol / L calcium chloride at pH 3 to 5, the presence or absence of gelation was confirmed visually, but no gelation occurred.

[0096] (Application of test sample to rat brown adipose precursor cells) Rat brown adipose tissue precursor cells (hereinafter sometimes referred to as "brown adipocytes"), proliferation medium, differentiation induction medium, and adipocyte maintenance medium were obtained from Cosmobio, and 1.0 × 10 brown adipocytes were cultured. 5 cells / cm 2 96-well plate (for fatty acid β-oxidation activity evaluation) and 24-well plate (for mRNA gene expression analysis) The cells were seeded and cultured in a proliferation medium at 37°C under 5% CO2 for 3 days. After that, they were cultured in a differentiation induction medium for 2 days, and the test sample was added to the adipocyte maintenance medium at a final concentration of 1 mg / mL, and cultured for an additional 5 days. Cells were cultured in the same manner but with 1% (v / v) phosphate-buffered saline (PBS) without the test sample added, and used as a control. The cells to which the test samples were applied were subjected to evaluation of fatty acid β-oxidation activity and mRNA gene expression analysis.

[0097] (Method for evaluating fatty acid β-oxidation activity) The cells to which the test sample was applied were washed twice with HEPES Buffered Saline Solution (HBSS, PromoCell), and then treated with FAOBlue (registered trademark) (final concentration 20 μM, Funakoshi) and the test sample. The cells were cultured for 30 minutes in HBSS supplemented with PBS (PBS for the control). Afterwards, the fluorescence intensity (Ex 405 nm / Em 460 nm) was measured using a plate reader. The intensity was corrected by subtracting the fluorescence intensity of a control without FAOBlue®.

[0098] (Results of fatty acid β-oxidation activity) The evaluation results of fatty acid β-oxidation activity are shown in Table 1. Application of the test sample significantly increased fatty acid β-oxidation activity. Specifically, it was 1.22 times higher than the control.

[0099] [Table 1]

[0100] (mRNA gene expression analysis method) The cells to which the test sample was applied were washed twice with PBS, and total RNA was then recovered using NucleoSpin® RNA (Takara Bio). Complementary DNA was prepared from the total RNA using PrimeScript FAST RT reagent Kit with gDNA Eraser (Takara Bio), and the total RNA was purified using TB Green Real-time PCR was performed using Premix Ex TaqII FAST qPCR (Takara Bio). The gene expression levels of PGC-1α, UCP-1, and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) were quantitatively analyzed using the ELISA method. The expression levels of PGC-1α and UCP-1 were normalized by the expression level of GAPDH. The base sequences of the primers used for quantitative analysis of the gene expression levels of PGC-1α, UCP-1, and GAPDH are shown in Table 2.

[0101] [Table 2]

[0102] (Results of gene expression analysis of PGC-1α and UCP-1) The results of mRNA gene expression analysis in brown adipocytes are shown in Table 3. Application of the test sample significantly increased the mRNA gene expression levels of both PGC-1α and UCP-1. Specifically, the expression levels of PGC-1α were 1.54-fold higher than the control, and the expression levels of UCP-1 were 1.53-fold higher than the control.

[0103] [Table 3]

Claims

1. A composition for enhancing PGC-1α gene expression, comprising, as an active ingredient, a whey protein hydrolysate having the following physicochemical properties (1) to (3): (1) The whey protein hydrolysate has an average molecular chain length of 2 to 10. (2) The fraction of whey protein hydrolysate having a molecular weight of 5,000 to 10,000 daltons accounts for 8% or less of the total whey protein hydrolysate. (3) The amount of free amino acids relative to the total amount of amino acids in the whey protein hydrolysate is 10% or less.

2. A composition for enhancing UCP-1 gene expression, comprising, as an active ingredient, a whey protein hydrolysate having the following physicochemical properties (1) to (3): (1) The whey protein hydrolysate has an average molecular chain length of 2 to 10. (2) The fraction of whey protein hydrolysate having a molecular weight of 5,000 to 10,000 daltons accounts for 8% or less of the total whey protein hydrolysate. (3) The amount of free amino acids relative to the total amount of amino acids in the whey protein hydrolysate is 10% or less.

3. A composition for enhancing fatty acid β-oxidation activity, comprising, as an active ingredient, a whey protein hydrolysate having the following physicochemical properties (1) to (3): (1) The whey protein hydrolysate has an average molecular chain length of 2 to 10. (2) The fraction of whey protein hydrolysate having a molecular weight of 5,000 to 10,000 daltons accounts for 8% or less of the total whey protein hydrolysate. (3) The amount of free amino acids relative to the total amount of amino acids in the whey protein hydrolysate is 10% or less.

4. A composition for promoting mitochondrial biogenesis, comprising, as an active ingredient, a whey protein hydrolysate having the following physicochemical properties (1) to (3): (1) The whey protein hydrolysate has an average molecular chain length of 2 to 10. (2) The fraction of whey protein hydrolysate having a molecular weight of 5,000 to 10,000 daltons accounts for 8% or less of the total whey protein hydrolysate. (3) The amount of free amino acids relative to the total amount of amino acids in the whey protein hydrolysate is 10% or less.

5. A composition for promoting energy consumption, comprising, as an active ingredient, a whey protein hydrolysate having the following physicochemical properties (1) to (3): (1) The whey protein hydrolysate has an average molecular chain length of 2 to 10. (2) The fraction of whey protein hydrolysate having a molecular weight of 5,000 to 10,000 daltons accounts for 8% or less of the total whey protein hydrolysate. (3) The amount of free amino acids relative to the total amount of amino acids in the whey protein hydrolysate is 10% or less.

6. A composition for use in the prevention or treatment of one or more conditions selected from the group consisting of mitochondrial dysfunction, insulin resistance, impaired glucose tolerance, adipose tissue hypertrophy, adipose tissue fibrosis, fatty liver, dyslipidemia, hypertension, heart disease, arteriosclerosis due to hypercholesterolemia, arteriosclerosis due to dyslipidemia, diabetes, obesity, metabolic syndrome, and renal fibrosis, comprising as an active ingredient a whey protein hydrolysate having the physicochemical properties (1) to (3) below. (1) The whey protein hydrolysate has an average molecular chain length of 2 to 10. (2) The fraction of whey protein hydrolysate having a molecular weight of 5,000 to 10,000 daltons accounts for 8% or less of the total whey protein hydrolysate. (3) The amount of free amino acids relative to the total amount of amino acids in the whey protein hydrolysate is 10% or less.

7. The composition according to any one of claims 1 to 6, which is a food or drink composition.

8. The composition according to any one of claims 1 to 6, which is a pharmaceutical composition.

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