Lipid metabolism promoter
Epigallocatechin-4'-O-methyl ether gallate (EGCg-4'-O-Me) addresses the need for a material that enhances lipid metabolism and β-oxidation by promoting the expression of key genes, resulting in improved energy production and exercise performance.
Patent Information
- Application Number
- JP2021112188
- Authority / Receiving Office
- JP · JP
- Patent Type
- Patents
- Current Assignee / Owner
- Filing Date
- 2021-07-06
- Publication Date
- 2025-06-10
- Estimated Expiration
- 2041-07-06
AI Technical Summary
Current technologies lack an effective material that promotes lipid metabolism, particularly β-oxidation, and the expression of related genes such as ACOX1 and ACADS, which are crucial for energy production and exercise performance.
Epigallocatechin-4'-O-methyl ether gallate (EGCg-4'-O-Me) is identified as a compound that significantly promotes the expression of lipid metabolism-related genes and enhances β-oxidation, offering a potential solution for improving lipid metabolism and energy supply.
EGCg-4'-O-Me effectively increases the expression of ACOX1 and ACADS genes, thereby promoting lipid metabolism and β-oxidation, which can lead to improved energy production and exercise performance.
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Abstract
Description
Technical Field
[0001] The present invention relates to a lipid metabolism promoter.
Background Art
[0002] In a living body, lipids not only serve as constituents of cell membranes, nuclear membranes, hormones, etc., but also function as subcutaneous fat for protecting organs, and are utilized as an important energy source along with sugars. Lipids are ingested and absorbed through diet, and are also synthesized in the body. Excess lipids are stored in adipocytes that make up adipose tissue. On the other hand, in a state of energy deficiency such as fasting or exercise, fatty acids derived from diet or accumulated in the body are secreted into the blood. Fatty acids circulate in the body in a state of binding to albumin, and are taken up by cells of various tissues including skeletal muscle and utilized as an energy source.
[0003] Fatty acids taken up by cells are converted by acyl-CoA synthetase into a thioester with coenzyme A, i.e., acyl-CoA, and are decomposed by the β-oxidation system in mitochondria and peroxisomes. In mitochondria, since acyl-CoA cannot pass through the inner mitochondrial membrane as it is, it is converted into acylcarnitine by carnitine palmitoyltransferase I present on the outer mitochondrial membrane. Acylcarnitine is transported into the mitochondrial matrix by carnitine acylcarnitine translocase and is further reconverted into acyl-CoA by carnitine palmitoyltransferase II. Thereafter, acyl-CoA repeatedly undergoes β-oxidation consisting of a four-step enzymatic reaction to generate a large number of FADH 2 , NADH and acetyl-CoA. In the first step of β-oxidation, acyl-CoA dehydrogenase introduces a double bond at the β-position of acyl-CoA, and coenzyme FAD is converted into FADH 2It is converted. In peroxisomes, acyl-CoA oxidase is used instead of acyl-CoA dehydrogenase. In the second step, 2-enoyl-CoA hydratase adds water to the double bond at the β-position of acyl-CoA to produce 3-hydroxyacyl-CoA. In the third step, 3-hydroxyacyl-CoA dehydrogenase produces 3-ketoacyl-CoA and + coenzyme NAD is converted to NADH. In the fourth step, 3-ketoacyl-CoA thiolase causes the addition of CoA-SH and the cleavage between the α- and β-carbons to produce acetyl-CoA and acyl-CoA with two fewer carbon atoms. Such acyl-CoA undergoes a series of β-oxidation reactions again. Finally, fatty acids are decomposed into acetyl-CoA units and are broken down to H 2 O and CO 2 through the TCA cycle. Also, FADH 2 and NADH generated during the reaction process are used for ATP production through the electron transport system and oxidative phosphorylation. Thus, β-oxidation plays an important role in energy metabolism that oxidizes fatty acids to supply energy. If lipid metabolism, especially β-oxidation, can be promoted, it will lead to effects such as improved energy production, increased energy supply to skeletal muscles, etc., and ultimately improved exercise performance.
[0004] So far, it has been reported that epigallocatechin gallate (EGCg), a major polyphenol contained in tea leaves, promotes lipid metabolism (Non-Patent Document 1). Also, Benifuuki, a type of tea variety, contains epigallocatechin-3-(3”-O-methyl) gallate (EGCg-3”-O-Me) in which the hydrogen atom of the hydroxyl group at the 3” position of the D ring of EGCg is substituted with a methyl group. It has been reported that such Benifuuki tea leaves have an effect of suppressing weight gain, suppressing the increase in subcutaneous fat weight, and suppressing the increase in visceral adipose tissue weight (Non-Patent Document 2). However, Non-Patent Document 2 does not directly mention the effect of EGCg-3”-O-Me on lipid metabolism. On the other hand, there is no report on the effect of epigallocatechin-4'-O-methyl ether gallate (EGCg-4'-O-Me), in which the hydrogen atom of the hydroxyl group at the 4'-position of the B ring of EGCg is substituted with a methyl group, on obesity and lipid metabolism.
Prior Art Documents
Non-Patent Documents
[0005]
Non-Patent Document 1
Non-Patent Document 2
Summary of the Invention
Problems to be Solved by the Invention
[0006] The present invention relates to providing a material effective for promoting lipid metabolism, which has an excellent effect of promoting the expression of lipid metabolism-related genes.
Means for Solving the Problems
[0007] In view of the above problems, the present inventors conducted studies and found that epigallocatechin-4'-O-methyl ether gallate significantly promotes the expression of lipid metabolism-related genes and exhibits a lipid metabolism-promoting effect.
[0008] That is, the present invention provides a lipid metabolism promoter containing epigallocatechin-4'-O-methyl ether gallate as an active ingredient. The present invention also provides a β-oxidation promoter containing epigallocatechin-4'-O-methyl ether gallate as an active ingredient. The present invention also provides at least one expression promoter selected from the group consisting of ACOX1 and ACADS, which contains epigallocatechin-4'-O-methyl ether gallate as an active ingredient. The present invention also provides a food for promoting lipid metabolism, which contains epigallocatechin-4'-O-methyl ether gallate as an active ingredient. The present invention also provides a food for promoting β-oxidation, which contains epigallocatechin-4'-O-methyl ether gallate as an active ingredient. The present invention also provides a food for promoting the expression of at least one selected from the group consisting of ACOX1 and ACADS, which contains epigallocatechin-4'-O-methyl ether gallate as an active ingredient.
Advantages of the Invention
[0009] According to the present invention, there are provided a pharmaceutical, a quasi-drug, a food, or a material and method used in a pharmaceutical, a quasi-drug or a food, which has an action of promoting the expression of lipid metabolism-related genes and is useful for promoting lipid metabolism, β-oxidation, etc. Therefore, according to the present invention, it is possible to promote the expression of lipid metabolism-related genes and promote lipid metabolism and β-oxidation.
Brief Description of the Drawings
[0010]
Figure 1
Modes for Carrying Out the Invention
[0011] Epigallocatechin-4'-O-methyl ether gallate (EGCg-4'-O-Me) used in the present invention is a compound represented by the following formula, and is a compound in which the hydrogen atom of the hydroxyl group at the 4'-position of the B ring of epigallocatechin gallate (EGCg) is substituted with a methyl group.
[0012]
Chemical Formula
[0013] EGCg-4'-O-Me is commercially available. Examples of commercially available products include (-)-Epigallocatechin-4'-O-methylether gallate (Nagara Science Co., Ltd.), (-)-Epigallocatechin-4'-O-methylether gallate (FUJIFILM Wako Pure Chemical Corporation), (-)-Epigallocatechin-4'-O-methylether gallate (Nacalai Tesque, Inc.), (-)-Epigallocatechin-4'-O-methylether gallate (Kishida Chemical Co., Ltd.), and the like.
[0014] Alternatively, EGCg-4'-O-Me may be chemically synthesized by a known method or produced by substituting the hydrogen atom of the hydroxyl group at the 4'-position of the B ring of EGCg with a methyl group using an enzyme. Examples of the chemical synthesis method include the methods described in International Publication No. 2010 / 067599, the report by Sheng Wan et al. (Tetrahedron, 2006, 62, 5897-5904), and the like. Examples of the method using an enzyme include the method using catechol-O-methyltransferase (COMT) extracted from the livers of rats, pigs, cows, etc., and the method using a methyltransferase derived from a plant as described in JP-A-2006-141242.
[0015] As shown in the following examples, when EGCg-4’-O-Me was added to human skeletal muscle cells, the expression of acyl-CoA oxidase (ACOX1) gene and acyl-CoA dehydrogenase (ACADS) gene, which are genes related to lipid metabolism, was significantly increased. In the lipid metabolism of the living body, ACOX1 is a flavin enzyme that catalyzes the reaction of introducing a double bond at the β-position of acyl-CoA in the β-oxidation system of fatty acids in peroxisomes, and is the rate-limiting enzyme of peroxisomal β-oxidation. ACADS is a flavin enzyme that catalyzes the reaction of introducing a double bond at the β-position of acyl-CoA in the β-oxidation system of fatty acids in mitochondria, and is one of the main enzymes in β-oxidation in mitochondria. The effect of EGCg-4’-O-Me was far superior to that of epigallocatechin gallate (EGCg), which is known as the main component of tea catechins, or epigallocatechin-3-(3”-O-methyl) gallate (EGCg-3”-O-Me) in which the hydrogen atom of the hydroxyl group at the 3” position of the D ring of EGCg contained in a specific variety of tea leaves is substituted with a methyl group. Therefore, EGCg-4’-O-Me can be used to promote the expression of lipid metabolism-related genes, to promote lipid metabolism, or to promote β-oxidation. For example, it can be used as a lipid metabolism promoter (preferably a promoter for lipid metabolism in skeletal muscle), a β-oxidation promoter (preferably a promoter for β-oxidation in skeletal muscle), or at least one expression promoter selected from the group consisting of ACOX1 and ACADS, and can also be used for producing the lipid metabolism promoter, the β-oxidation promoter, or at least one expression promoter selected from the group consisting of ACOX1 and ACADS.
[0016] In addition, the use may be in a human or non-human animal, or a specimen derived therefrom, preferably for human use. It may be a therapeutic use or a non-therapeutic use. Here, "non-therapeutic" refers to a concept that does not include medical acts, that is, a concept that does not include methods of operating on, treating or diagnosing a human being. More specifically, it is a concept that does not include methods by which a doctor or a person receiving instructions from a doctor performs an operation, treatment or diagnosis on a human being.
[0017] Here, "lipid metabolism" means the metabolism of lipids in a living body, particularly the breakdown of lipids for energy production. "Promotion of lipid metabolism" means inducing or promoting the metabolism of lipids derived from dietary sources or lipids accumulated in the body, particularly the breakdown of lipids for energy production. The "lipid metabolism-related gene" may be any gene involved in the lipid metabolism pathway, preferably a gene involved in the lipid breakdown pathway, more preferably a gene involved in β-oxidation. Examples of such genes include, but are not limited to, ACOX1 (Gene ID: 51), ACADS (Gene ID: 35), etc. In addition, the gene names (Gene Symbol) and Gene IDs disclosed in this specification follow the Official Symbol and Gene ID described in NCBI ([www.ncbi.nlm.nih.gov / ]). "Promotion of expression of lipid metabolism-related genes" includes inducing or promoting the transcription of mRNA from lipid metabolism-related genes and inducing or promoting the translation of mRNA derived from lipid metabolism-related genes. "Promotion of β-oxidation" means inducing or promoting the oxidation of fatty acids derived from dietary sources or lipids accumulated in the body. "Promotion of expression of at least one selected from the group consisting of ACOX1 and ACADS" includes inducing or promoting the transcription of mRNA from at least one gene selected from the group consisting of the ACOX1 gene and the ACADS gene, and inducing or promoting the translation of mRNA derived from at least one gene selected from the group consisting of the ACOX1 gene and the ACADS gene.
[0018] The lipid metabolism promoter, β-oxidation promoter, and at least one expression promoter selected from the group consisting of ACOX1 and ACADS (hereinafter referred to as "lipid metabolism promoter, etc.") of the present invention is useful as a pharmaceutical, quasi-drug, or food that exhibits each effect of promoting lipid metabolism, promoting β-oxidation, and promoting the expression of at least one selected from the group consisting of ACOX1 and ACADS, or as a material or preparation for blending into a quasi-drug or food.
[0019] The dosage form of the above-mentioned pharmaceuticals (including quasi-drugs) may be, for example, any of injections, suppositories, inhalants, transdermal absorbents, various external preparations, tablets, capsules, granules, powders, syrups, etc., and the administration form may be either oral administration (for internal use) or parenteral administration (for external use, injection), but oral administration is preferred. Preparations of such various dosage forms can be prepared according to conventional methods by combining EGCg-4'-O-Me alone or with pharmaceutically acceptable carriers (such as excipients, binders, extenders, disintegrants, surfactants, lubricants, dispersants, buffers, preservatives, flavoring agents, fragrances, coating agents, diluents, etc.) and other pharmaceutically active ingredients as appropriate.
[0020] The content of EGCg-4'-O-Me in the above-mentioned pharmaceuticals (including quasi-drugs) is not particularly limited, but is preferably 0.01% by mass or more, more preferably 0.1% by mass or more, still more preferably 1% by mass or more, and preferably 100% by mass or less, more preferably 90% by mass or less, still more preferably 70% by mass or less. Further, examples of the content include 0.01 to 100% by mass, 0.01 to 90% by mass, 0.01 to 70% by mass, 0.1 to 100% by mass, 0.1 to 90% by mass, 0.1 to 70% by mass, 1 to 100% by mass, 1 to 90% by mass, and 1 to 70% by mass.
[0021] In addition to general foods, the above-mentioned foods include foods with the concept of promoting lipid metabolism, promoting β-oxidation, etc., and foods, functional foods, foods for patients, foods for specified health uses, foods with functional claims, and supplements that display the purpose as necessary.
[0022] Food includes beverages, and the food can be rephrased as food and drink. The form of the food can be solid, semi-solid or liquid. Examples of food include breads, noodles, confectioneries such as cookies, jellies, dairy products, frozen foods, instant foods, starch processed products, processed meat products, other processed foods, beverages such as tea and coffee beverages, fruit beverages, carbonated beverages, jelly-like beverages, soups, seasonings, dietary supplements, etc., and their raw materials. Also, the food may be in the form of tablets, pills, capsules, liquids, syrups, powders, granules, etc., like supplements and similar to the above oral administration preparations.
[0023] The above food can be prepared according to a conventional method by appropriately combining EGCg-4’-O-Me with any food material or an additive acceptable in food (such as a solvent, plasticizer, oil, emulsifier, preservative, fragrance, sweetener, stabilizer, colorant, ultraviolet absorber, antioxidant, humectant, thickener, fixing agent, dispersant, wetting agent, etc.).
[0024] The content of EGCg-4’-O-Me in the above food is not particularly limited, but is preferably 0.01% by mass or more, more preferably 0.05% by mass or more, still more preferably 0.1% by mass or more, still more preferably 0.5% by mass or more, and is preferably 10% by mass or less, more preferably 5% by mass or less, still more preferably 1% by mass or less. Further, examples of the content include 0.01 - 10% by mass, 0.01 - 5% by mass, 0.01 - 1% by mass, 0.05 - 10% by mass, 0.05 - 5% by mass, 0.05 - 1% by mass, 0.1 - 10% by mass, 0.1 - 5% by mass, 0.1 - 1% by mass, 0.5 - 10% by mass, 0.5 - 5% by mass, and 0.5 - 1% by mass.
[0025] In the present invention, the dosage and dosing schedule of EGCg-4'-O-Me may be appropriately determined by those skilled in the art according to the species, body weight, sex, age, condition, or other factors of the subject. By way of non-limiting example, in the case of oral administration, the dosage of EGCg-4'-O-Me according to the present invention per adult per day is preferably 100 mg / 60 kg body weight or more, more preferably 250 mg / 60 kg body weight or more, and preferably 3000 mg / 60 kg body weight or less, more preferably 2000 mg / 60 kg body weight or less, still more preferably 1000 mg / 60 kg body weight or less, and even more preferably 600 mg / 60 kg body weight or less. Further, as examples of such dosages, 100 - 3000 mg / 60 kg body weight, 100 - 2000 mg / 60 kg body weight, 100 - 1000 mg / 60 kg body weight, 100 - 600 mg / 60 kg body weight, 250 - 3000 mg / 60 kg body weight, 250 - 2000 mg / 60 kg body weight, 250 - 1000 mg / 60 kg body weight, and 250 - 600 mg / 60 kg body weight may be mentioned. It is preferable to administer the above dosages, for example, once a day, or divided into two or more times a day, such as two or three times a day.
[0026] In addition, the subject of administration or ingestion is not particularly limited as long as it is an animal that needs or desires it, but examples include humans who need or desire to promote lipid metabolism, promote β-oxidation, etc. Further examples of the subject of ingestion include humans who need or desire to improve energy production, and humans who need or desire to improve exercise performance.
[0027] The present invention also includes, as exemplary embodiments, the following substances, production methods, uses, methods, etc. However, the present invention is not limited to these embodiments.
[0028] [1] A lipid metabolism promoter containing epigallocatechin-4'-O-methyl ether gallate as an active ingredient. [2] The agent according to [1], wherein the lipid metabolism is lipid metabolism in skeletal muscle. [3] A β-oxidation promoter containing epigallocatechin-4'-O-methyl ether gallate as an active ingredient. 〔4〕At least one expression promoter selected from the group consisting of ACOX1 and ACADS, having epigallocatechin-4'-O-methyl ether gallate as an active ingredient. 〔5〕Preferably, the agent is a pharmaceutical or quasi-drug, and contains 0.01 to 100% by mass, 0.01 to 90% by mass, 0.01 to 70% by mass, 0.1 to 100% by mass, 0.1 to 90% by mass, 0.1 to 70% by mass, 1 to 100% by mass, 1 to 90% by mass, or 1 to 70% by mass of the epigallocatechin-4'-O-methyl ether gallate. The agent according to any one of 〔1〕 to 〔4〕. 〔6〕Preferably, the agent is a food, and contains 0.01 to 10% by mass, 0.01 to 5% by mass, 0.01 to 1% by mass, 0.05 to 10% by mass, 0.05 to 5% by mass, 0.05 to 1% by mass, 0.1 to 10% by mass, 0.1 to 5% by mass, 0.1 to 1% by mass, 0.5 to 10% by mass, 0.5 to 5% by mass, or 0.5 to 1% by mass of the epigallocatechin-4'-O-methyl ether gallate. The agent according to any one of 〔1〕 to 〔4〕. 〔7〕Preferably, the agent is an oral preparation. The agent according to any one of 〔1〕 to 〔6〕.
[0029] 〔8〕Use of epigallocatechin-4'-O-methyl ether gallate for the manufacture of a lipid metabolism promoter. 〔9〕The use according to 〔8〕, wherein the lipid metabolism is lipid metabolism in skeletal muscle. 〔10〕Use of epigallocatechin-4'-O-methyl ether gallate for the manufacture of a β-oxidation promoter. 〔11〕Use of epigallocatechin-4'-O-methyl ether gallate for the manufacture of at least one expression promoter selected from the group consisting of ACOX1 and ACADS. 〔12〕Preferably, the agent is a pharmaceutical or quasi-drug, and contains 0.01 to 100% by mass, 0.01 to 90% by mass, 0.01 to 70% by mass, 0.1 to 100% by mass, 0.1 to 90% by mass, 0.1 to 70% by mass, 1 to 100% by mass, 1 to 90% by mass, or 1 to 70% by mass of the epigallocatechin-4'-O-methyl ether gallate. The use according to any one of 〔8〕 to 〔11〕. [(13)] Preferably, the agent is a food, and contains 0.01 to 10% by mass, 0.01 to 5% by mass, 0.01 to 1% by mass, 0.05 to 10% by mass, 0.05 to 5% by mass, 0.05 to 1% by mass, 0.1 to 10% by mass, 0.1 to 5% by mass, 0.1 to 1% by mass, 0.5 to 10% by mass, 0.5 to 5% by mass, or 0.5 to 1% by mass of the epigallocatechin-4'-O-methyl ether gallate, and is the use according to any one of [(8)] to [(11)]. [(14)] Preferably, the agent is an oral agent, and is the use according to any one of [(8)] to [(13)].
[0030] [(15)] Use of epigallocatechin-4'-O-methyl ether gallate for promoting lipid metabolism. [(16)] The use according to [(15)], wherein the lipid metabolism is lipid metabolism in skeletal muscle. [(17)] Use of epigallocatechin-4'-O-methyl ether gallate for promoting β-oxidation. [(18)] Use of epigallocatechin-4'-O-methyl ether gallate for promoting the expression of at least one selected from the group consisting of ACOX1 and ACADS. [(19)] Preferably, it is used in the form of a pharmaceutical or quasi-drug containing 0.01 to 100% by mass, 0.01 to 90% by mass, 0.01 to 70% by mass, 0.1 to 100% by mass, 0.1 to 90% by mass, 0.1 to 70% by mass, 1 to 100% by mass, 1 to 90% by mass, or 1 to 70% by mass of the epigallocatechin-4'-O-methyl ether gallate, and is the use according to any one of [(15)] to [(18)]. [(20)] Preferably, it is used in the form of a food containing 0.01 to 10% by mass, 0.01 to 5% by mass, 0.01 to 1% by mass, 0.05 to 10% by mass, 0.05 to 5% by mass, 0.05 to 1% by mass, 0.1 to 10% by mass, 0.1 to 5% by mass, 0.1 to 1% by mass, 0.5 to 10% by mass, 0.5 to 5% by mass, or 0.5 to 1% by mass of the epigallocatechin-4'-O-methyl ether gallate, and is the use according to any one of [(15)] to [(18)]. [(21)] Preferably, the epigallocatechin-4'-O-methyl ether gallate is orally administered, and is the use according to any one of [(15)] to [(20)].
[0031] 〔22〕Epigallocatechin-4'-O-methyl ether gallate for use in promoting lipid metabolism. 〔23〕The epigallocatechin-4'-O-methyl ether gallate according to
[22] , wherein the lipid metabolism is lipid metabolism in skeletal muscle. 〔24〕Epigallocatechin-4'-O-methyl ether gallate for use in promoting β-oxidation. 〔25〕Epigallocatechin-4'-O-methyl ether gallate for use in promoting the expression of at least one selected from the group consisting of ACOX1 and ACADS. 〔26〕Preferably, the pharmaceutical or quasi-drug contains 0.01 to 100% by mass, 0.01 to 90% by mass, 0.01 to 70% by mass, 0.1 to 100% by mass, 0.1 to 90% by mass, 0.1 to 70% by mass, 1 to 100% by mass, 1 to 90% by mass, or 1 to 70% by mass of the epigallocatechin-4'-O-methyl ether gallate. The epigallocatechin-4'-O-methyl ether gallate according to any one of
[22] to
[25] . 〔27〕Preferably, the food contains 0.01 to 10% by mass, 0.01 to 5% by mass, 0.01 to 1% by mass, 0.05 to 10% by mass, 0.05 to 5% by mass, 0.05 to 1% by mass, 0.1 to 10% by mass, 0.1 to 5% by mass, 0.1 to 1% by mass, 0.5 to 10% by mass, 0.5 to 5% by mass, or 0.5 to 1% by mass of the epigallocatechin-4'-O-methyl ether gallate. The epigallocatechin-4'-O-methyl ether gallate according to any one of
[22] to
[25] . 〔28〕Preferably, the epigallocatechin-4'-O-methyl ether gallate according to any one of
[22] to
[27] is orally administered. 〔29〕Preferably, the dosage of epigallocatechin-4'-O-methyl ether gallate per adult per day is 100 - 3000 mg / 60 kg body weight, 100 - 2000 mg / 60 kg body weight, 100 - 1000 mg / 60 kg body weight, 100 - 600 mg / 60 kg body weight, 250 - 3000 mg / 60 kg body weight, 250 - 2000 mg / 60 kg body weight, 250 - 1000 mg / 60 kg body weight, or 250 - 600 mg / 60 kg body weight, and it is the epigallocatechin-4'-O-methyl ether gallate according to any one of 〔22〕~〔28〕. 〔30〕Preferably, the epigallocatechin-4'-O-methyl ether gallate of the dosage is administered once a day, or administered in divided doses 2 or 3 or more times a day, and it is the epigallocatechin-4'-O-methyl ether gallate according to 〔29〕.
[0032] 〔31〕A method for promoting lipid metabolism, which comprises administering an effective amount of epigallocatechin-4'-O-methyl ether gallate to a subject in need thereof. 〔32〕The method according to 〔31〕, wherein the lipid metabolism is lipid metabolism in skeletal muscle. 〔33〕A method for promoting β-oxidation, which comprises administering an effective amount of epigallocatechin-4'-O-methyl ether gallate to a subject in need thereof. 〔34〕A method for promoting the expression of at least one selected from the group consisting of ACOX1 and ACADS, which comprises administering an effective amount of epigallocatechin-4'-O-methyl ether gallate to a subject in need thereof. 〔35〕Preferably, the administration is oral administration, and it is the method according to any one of 〔31〕~〔34〕. 〔36〕Preferably, the dosage of epigallocatechin-4'-O-methyl ether gallate per adult per day is 100 - 3000 mg / 60 kg body weight, 100 - 2000 mg / 60 kg body weight, 100 - 1000 mg / 60 kg body weight, 100 - 600 mg / 60 kg body weight, 250 - 3000 mg / 60 kg body weight, 250 - 2000 mg / 60 kg body weight, 250 - 1000 mg / 60 kg body weight, or 250 - 600 mg / 60 kg body weight, and the method according to any one of 〔31〕 - 〔35〕. 〔37〕Preferably, the epigallocatechin-4'-O-methyl ether gallate of the dosage is administered once a day, or administered in two or more divided doses a day, and the method according to 〔36〕.
[0033] 〔38〕A food for promoting lipid metabolism containing epigallocatechin-4'-O-methyl ether gallate as an active ingredient. 〔39〕The food according to 〔38〕, wherein the lipid metabolism is lipid metabolism in skeletal muscle. 〔40〕A food for promoting β-oxidation containing epigallocatechin-4'-O-methyl ether gallate as an active ingredient. 〔41〕A food for promoting the expression of at least one selected from the group consisting of ACOX1 and ACADS containing epigallocatechin-4'-O-methyl ether gallate as an active ingredient. 〔42〕Preferably, the food according to any one of 〔38〕 - 〔41〕 contains the epigallocatechin-4'-O-methyl ether gallate in an amount of 0.01 - 10% by mass, 0.01 - 5% by mass, 0.01 - 1% by mass, 0.05 - 10% by mass, 0.05 - 5% by mass, 0.05 - 1% by mass, 0.1 - 10% by mass, 0.1 - 5% by mass, 0.1 - 1% by mass, 0.5 - 10% by mass, 0.5 - 5% by mass, or 0.5 - 1% by mass.
Examples
[0034] Hereinafter, the present invention will be described more specifically with reference to examples. However, the technical scope of the present invention is not limited to these examples.
[0035] Example 1: Effect of Methylated Catechins on Lipid Metabolism in Human Skeletal Muscle Cells Human iPS cell-derived differentiated cells, iCell Skeletal Muscle Cells (8×10 6 cells / well, FUJIFILM Cellular Dynamics, INC) were seeded in a 96-well plate with a medium prepared by adding 1 mM 8-bromoadenosine 3’,5’-cyclic monophosphate (B5386-5MG, Sigma-Aldrich), 20 μM CHIR99021 (4423 / 10, Tocris Bioscience), 1 μM Dorsomorphin (P5499-5MG, Sigma-Aldrich), and 5 mL KnockOut Serum Replacement (10828010, Invitrogen) to MEM Alpha (12561056, gibco) (1×10 5 cells / well). The culture plate used was coated with Fibronectin (11051407001, Sigma-Aldrich). The cells were cultured at 37°C under 5% CO 2 2 conditions, and the medium was changed on the 1st and 3rd days after seeding. On the 4th day after seeding, the medium was replaced with a medium containing 0.1 μM tea catechins (EGCg, EGCg-4’-O-Me, EGCg-3”-O-Me, Nagara Science Co., Ltd.) or a medium without tea catechins (control), and the cells were collected from the medium 24 hours later. RNA was extracted from the collected cells using the RNeasy Plus Micro Kit (QIAGEN), cDNA synthesis was performed using the High-Capacity RNA-to-cDNA Kit (Applied Biosystems), and then the expression of the following lipid metabolism-related genes was quantified by Realtime PCR (Taqman gene expression, Applied Biosystems). The expression level of each gene was corrected using the gene expression level of RPLP0 as an internal standard. Statistical analysis was performed by t-test one-way ANOVA with n = 3 - 4 for each group (vs control group), and * indicates <p = 0.05.
[0036] Lipid metabolism-related genes (the numbers in parentheses indicate the Assay IDs of Taqman gene expression assay) ACOX1: acyl-CoA oxidase 1 (Hs01074241_m1) ACADS: acyl-CoA dehydrogenase, C-2 to C-3 short chain (Hs00163506_m1) RPLP0: ribosomal protein lateral stalk subunit P0 (Hs00420895_gH)
[0037] The results are shown in Figure 1. In the EGCg-4’-O-Me addition group, the gene expressions of ACOX1 and ACADS were significantly increased compared with the control group. The gene expressions of ACOX1 and ACADS in the EGCg-4’-O-Me addition group were also much higher compared with those in the EGCg addition group and the EGCg-3”-O-Me addition group. Since ACOX1 and ACADS are lipid metabolism-related genes, it was shown that EGCg-4’-O-Me promoted lipid metabolism.
Claims
**Claim 1** A lipid metabolism promoter containing epigallocatechin-4'-O-methyl ether gallate as an active ingredient. **Claim 2** The lipid metabolism promoter according to Claim 1, wherein the lipid metabolism is lipid metabolism in skeletal muscle. **Claim 3** A β-oxidation promoter containing epigallocatechin-4'-O-methyl ether gallate as an active ingredient. **Claim 4** An expression promoter for at least one selected from the group consisting of ACOX1 and ACADS, containing epigallocatechin-4'-O-methyl ether gallate as an active ingredient. **Claim 5** A food for promoting lipid metabolism containing epigallocatechin-4'-O-methyl ether gallate as an active ingredient. **Claim 6** The food for promoting lipid metabolism according to Claim 5, wherein the lipid metabolism is lipid metabolism in skeletal muscle. **Claim 7** A food for promoting β-oxidation containing epigallocatechin-4'-O-methyl ether gallate as an active ingredient. **Claim 8** A food for promoting the expression of at least one selected from the group consisting of ACOX1 and ACADS, containing epigallocatechin-4'-O-methyl ether gallate as an active ingredient.
Citation Information
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