Agent for promoting energy consumption

Abstract

The present invention addresses the problem of providing: an excellent agent that has an energy consumption promoting action, suppresses an increase in body weight and body fat percentage, and / or can contribute to prevention or amelioration of obesity; and a pharmaceutical composition or a food composition containing the agent. The problem can be solved by using a compound represented by formula (A).　

Description

Energy consumption promoter

[0001] The present invention relates to an energy consumption promoter, a lipid burning promoter, a thermogenesis promoter, a weight gain inhibitor, an agent for inhibiting or reducing an increase in body fat percentage, a muscle-building agent, an agent for preventing or ameliorating obesity, an agent for inhibiting or reducing an increase in total cholesterol amount, etc.

[0002] Obesity is a condition in which ingested energy such as carbohydrates and lipids is excessively stored as fat under the skin and around the internal organs, resulting in a higher body weight than normal.In recent years, the concept of metabolic syndrome has been attracting attention.This is a condition that is based on the excessive accumulation of visceral fat (obesity) and is prone to the development of arteriosclerosis, accompanied by impaired glucose tolerance (hyperglycemia), high triglycerides (hyperlipidemia), and high blood pressure, and is a condition that increases the risk of developing lifestyle-related diseases.

[0003] In recent years, the number of people suffering from obesity and metabolic syndrome has been increasing due to overnutrition and lack of exercise. The increase in the number of people suffering from obesity and metabolic syndrome can lead to an increase in medical expenses, and obesity and metabolic syndrome have become major problems not only in Japan but also on a global scale.

[0004] Obesity is induced when the amount of energy intake exceeds the amount of energy expenditure. Therefore, in order to improve obesity, it is possible to reduce the amount of energy intake from fats, etc., or to promote the body's metabolism in some way to increase the amount of energy expenditure.

[0005] Substances that promote energy consumption have been reported, such as those derived from natural products, such as rice bran extract (Patent Document 1) and licorice extract (Patent Document 2). While natural products may be preferable in terms of safety when taken over a long period of time, they have problems such as unstable quality and the risk of problems due to impurities. Therefore, compounds that can be chemically synthesized are easier to use as active ingredients. However, in the case of compounds, considering their industrial use, they must be able to be synthesized in large quantities at low cost. Furthermore, synthetic compounds that have not been consumed may pose safety concerns.

[0006] Meanwhile, a compound represented by the following formula (A) is known, and this compound is also known to have the effect of suppressing liver damage such as nonalcoholic steatohepatitis (NASH) (Patent Document 3). Because this compound is contained in a neutralized product of plum extract, it has been widely consumed, and technology for inexpensively synthesizing it in large quantities and separating and purifying it has also been established (Patent Document 4). Therefore, this compound is suitable for industrial use as an ingredient in foods, pharmaceuticals, etc.

[0007]

[0008] However, other effects of this compound were unknown.

[0009] JP 2012-020941 A JP 2018-58832 A WO2017 / 077707 WO2018 / 199040

[0010] An object of the present invention is to provide an excellent agent that has an effect of promoting energy consumption, suppresses increases in body weight and body fat percentage, and / or can contribute to the prevention or amelioration of obesity, as well as a pharmaceutical composition or food composition containing the same.

[0011] The present inventors have found that a compound represented by the following formula (A) (hereinafter, also referred to as "compound A") has an effect of promoting energy consumption, suppresses increases in body weight and body fat percentage, and can contribute to the prevention or improvement of obesity, etc., and have completed the present invention.

[0012]

[0013] That is, the present invention is as specified by the following features: [1] An energy consumption promoter containing a compound represented by the following formula (A) or a salt thereof as an active ingredient: [2] The energy consumption promoter according to the above item [1], which promotes energy consumption by increasing oxygen consumption. [3] A lipid burning promoter comprising a compound represented by the following formula (A) or a salt thereof as an active ingredient: [4] The lipid burning promoter according to the above [3] for promoting fat burning. [5] A thermogenesis promoter comprising a compound represented by the following formula (A) or a salt thereof as an active ingredient: [6] The thermogenesis promoter according to the above item [5] for increasing body temperature. [7] A weight gain inhibitor comprising a compound represented by the following formula (A) or a salt thereof as an active ingredient: [8] An agent for suppressing or reducing an increase in body fat percentage, comprising a compound represented by the following formula (A) or a salt thereof as an active ingredient: [9] The agent for suppressing or reducing an increase in body fat percentage according to the above item [8], for suppressing an increase in body fat mass.

[10] The agent for suppressing or reducing an increase in body fat percentage according to the above item [8], for suppressing the accumulation of body fat.

[11] A muscle-building agent comprising a compound represented by the following formula (A) or a salt thereof as an active ingredient:

[12] The muscle-building agent according to the above

[11] , for promoting an increase in muscle mass.

[13] An agent for preventing or ameliorating obesity, comprising a compound represented by the following formula (A) or a salt thereof as an active ingredient:

[14] An agent for suppressing an increase in or reducing total cholesterol, comprising a compound represented by the following formula (A) or a salt thereof as an active ingredient:

[15] A pharmaceutical composition or food composition containing the agent according to any one of [1] to

[14] above.

[0014] Other embodiments of the present invention include the following: 1) Use of compound A or a salt thereof for producing an energy consumption promoter, an oxygen consumption increaser, a lipid burning promoter, a fat burning promoter, a thermogenesis promoter, a body temperature elevating agent, a weight gain suppressor, an agent for suppressing or reducing an increase in body fat percentage, an agent for suppressing an increase in body fat mass, an agent for suppressing body fat accumulation, a muscle-building agent, an agent for promoting muscle mass increase, an agent for preventing or ameliorating obesity, or an agent for suppressing or reducing an increase in total cholesterol. 2-1) Compound A or a salt thereof for use in promoting energy consumption, increasing oxygen consumption, promoting lipid burning, promoting fat burning, promoting thermogenesis, increasing body temperature, suppressing weight gain, suppressing or reducing an increase in body fat percentage, suppressing an increase in body fat mass, suppressing body fat accumulation, building muscle, promoting an increase in muscle mass, preventing or ameliorating obesity, or suppressing or reducing an increase in total cholesterol. 2-2) Compound A or a salt thereof for use in preventing or treating hypothermia or poor circulation. 2-3) Compound A or a salt thereof for use in the prevention or treatment of obesity or metabolic syndrome. 2-4) Compound A or a salt thereof for use in the prevention or treatment of pathologies or diseases caused by obesity or metabolic syndrome. 2-5) Compound A or a salt thereof for use in the prevention or treatment of dyslipidemia. 2-6) Compound A or a salt thereof for use in the prevention or treatment of pathologies or diseases caused by an increase in total cholesterol. 3-1) A method for promoting energy consumption, increasing oxygen consumption, promoting lipid burning, promoting fat burning, promoting thermogenesis, increasing body temperature, suppressing weight gain, suppressing or reducing an increase in body fat percentage, suppressing an increase in body fat mass, suppressing body fat accumulation, building muscle, promoting an increase in muscle mass, preventing or ameliorating obesity, or suppressing an increase in or reducing total cholesterol, which method comprises administering an effective amount of compound A or a salt thereof to a subject in need thereof. 3-2) A method for preventing or treating hypothermia or sensitivity to cold, which comprises administering an effective amount of compound A or a salt thereof to a subject in need of such prevention or treatment. 3-3) A method for preventing or treating obesity or metabolic syndrome, which comprises administering an effective amount of compound A or a salt thereof to a subject in need of such prevention or treatment.3-4) A method for preventing or treating a pathology or disease caused by obesity or metabolic syndrome, which comprises administering an effective amount of compound A or a salt thereof to a subject in need of such prevention or treatment. 3-5) A method for preventing or treating dyslipidemia, which comprises administering an effective amount of compound A or a salt thereof to a subject in need of such prevention or treatment. 3-6) A method for preventing or treating a pathology or disease caused by an increase in total cholesterol, which comprises administering an effective amount of compound A or a salt thereof to a subject in need of such prevention or treatment.

[0015] According to the present invention, it is possible to provide agents, food compositions, pharmaceutical compositions, and the like that are useful for promoting energy consumption, promoting lipid burning, promoting thermogenesis, suppressing weight gain, suppressing or reducing an increase in body fat percentage, building muscle, preventing or ameliorating obesity, and / or suppressing or reducing an increase in total cholesterol level, etc.

[0016] 1 is a graph showing the calorie intake per day during the test period. In the figure, "CON" represents the "CON group" described in the Examples, and "Compound A" represents the "Compound A administration group" described in the Examples. The same applies to the following figures.

[0034] This is a graph showing the cumulative oxygen consumption over 24 hours after administration in the morning on day 82 of the test.

[0035] This is a graph showing the cumulative carbon dioxide production over 24 hours after administration in the morning on day 82 of the test.

[0036] This is a graph showing the cumulative energy consumption over 24 hours after administration in the morning on day 82 of the test.

[0037] This is a graph showing the cumulative amount of fat burned over 24 hours after administration in the morning on day 82 of the test.

[0038] This is a graph showing the rectal temperature before autopsy.

[0039] This is a graph showing the change in body weight during the test diet administration period.

[0040] This is a graph showing the body fat percentage and lean body mass percentage after 6 weeks, 9 weeks, and 12 weeks of ingestion of the test diet.

[0041] This is a graph showing the white fat weight (periepididymal fat, mesenteric fat, perirenal fat, interscapular fat) per body weight at autopsy. 1 is a graph showing the weights of the plantaris muscle, tibialis anterior muscle, and extensor digitorum longus muscle per body weight at autopsy, as well as the total weight of these three muscles. 2 is a graph showing the total cholesterol level in plasma at autopsy.

[0017] The energy consumption promoter, lipid burning promoter, thermogenesis promoter, weight gain inhibitor, agent for inhibiting or reducing an increase in body fat percentage, muscle-building agent, agent for preventing or ameliorating obesity, and agent for inhibiting or reducing an increase in total cholesterol amount (hereinafter, these may be collectively referred to as "agents of the present invention") of the present invention contain compound A or a salt thereof as an active ingredient.

[0018] Here, "containing as an active ingredient" means containing an effective amount. An effective amount means an amount sufficient to exert a desired effect in vivo. In addition, in the present invention, "using as an active ingredient" also means that other ingredients besides Compound A or a salt thereof may be contained, as long as the effects of the present invention are not impaired. The effective amount may vary depending on the condition of the subject, the severity of the pathology or disease, the animal species, age (months), sex, weight, etc. of the subject.

[0019] (Compound A) The compound A used in the present invention is a compound represented by the following formula (A).

[0020]

[0021] Since Compound A has two asymmetric carbons, it exists in four stereoisomers (i.e., Compound A whose stereostructure is the SS form, SR form, RS form, or RR form according to the RS representation), but in the present invention, there is no particular limitation on which stereoisomer is used. That is, in the present invention, any stereoisomer may be used alone, or a mixture of any two, three, or four of them in any ratio may be used. However, since Compound A whose stereostructure is the SS form and the RR form according to the RS representation is crystalline (WO 2018 / 199040) and is easier to handle, in the present invention, it is preferable to use Compound A whose stereostructure is the SS form or the RR form according to the RS representation, or to use a mixture of Compound A whose SS form and Compound A whose RR form are used as Compound A. Since Compound A is known to be contained in plum, plum extract, neutralized plum extract, etc., Compound A may be separated and purified from these by any method, chemically synthesized, or purchased as a commercially available product. However, since the amount of Compound A contained in plum, plum extract, neutralized plum extract, etc. is limited, using it as the active ingredient of the agent of the present invention may be inefficient, and since natural products may have unstable quality or impurity issues, it is preferable to use chemically synthesized Compound A or a salt thereof. That is, the agent of the present invention may be in an embodiment that does not contain or is substantially free of plum, plum extract, neutralized plum extract, etc. Furthermore, the agent of the present invention may be in an embodiment that does not contain or is substantially free of other natural products (e.g., plants of the Rosaceae family), natural product extracts (e.g., extracts of Rosaceae plants), neutralized natural product extracts (e.g., neutralized extracts of Rosaceae plants), etc. Here, "substantially free" means that it does not contain an effective amount and / or may contain an amount that is less than the effective amount. There are no particular limitations on the methods for chemically synthesizing, separating, and purifying Compound A or a salt thereof. For example, Compound A can be obtained by reacting citric acid with L-aspartic acid.When compound A or a salt thereof is chemically synthesized and then separated and purified, it is preferable to use, for example, the methods described in WO2017 / 07707 or WO2018 / 19940, because such methods enable the production of purified (highly purified) compound A or a salt thereof at low cost and in large quantities.

[0022] (Salt of Compound A) The salt of Compound A used in the present invention may be a metal salt or an amino acid salt of Compound A. The metal salt may be a metal salt selected from the group consisting of sodium salt, potassium salt, magnesium salt, and calcium salt, preferably calcium salt. The amino acid salt may be an amino acid salt selected from the group consisting of arginine salt, citrulline salt, ornithine salt, and histidine salt. The amino acid salt is preferably an L-amino acid salt.

[0023] (Energy Consumption Promoters and Oxygen Consumption Increasers) Compound A or a salt thereof has an energy consumption promoting effect and can therefore be suitably used as an active ingredient of an energy consumption promoter. In the present invention, "energy consumption" refers to the metabolism of nutrients (energy sources) such as lipids, proteins, and carbohydrates in various biological tissues and their conversion into chemical energy or thermal energy. "Metabolism" includes "combustion" or "oxidation." "Energy consumption promotion" refers to increasing energy consumption, for example, increasing the cumulative energy consumption over a certain period of time after administration of Compound A. For example, the cumulative energy consumption over 24 hours can be calculated from the average oxygen consumption and average carbon dioxide production over approximately 24 hours (e.g., 24 hours ± 1 hour) using the following formula: Cumulative energy expenditure (kcal / kg / day) = [{3.816 x average VO2 over approximately 24 hours (mL / min) + 1.231 x average VCO2 over approximately 24 hours (mL / min)} / body weight (kg) x 60 (min / h) x 24 (h))] / 1000 (cal / kcal) (VO2: oxygen consumption, VCO2: carbon dioxide production)

[0024] Administration of compound A or a salt thereof can increase cumulative energy expenditure over a certain period of time (e.g., 24 hours) compared to administration without compound A or a salt thereof. The increase is preferably 3% or more, more preferably 5% or more, even more preferably 7% or more, and particularly preferably 10% or more. Furthermore, the increase is preferably 20% or less, more preferably 18% or less, and particularly preferably 15% or less. Therefore, the increase can be 3-20%, 5-20%, 7-20%, 10-20%, 3-18%, 5-18%, 7-18%, 10-18%, 3-15%, 5-15%, 7-15%, 10-15%, etc.

[0025] Furthermore, since oxygen is required in the process of consuming energy, the energy consumption promoter of the present invention can also be used as an energy consumption promoter by increasing oxygen consumption (an energy consumption promoter that promotes energy consumption by increasing oxygen consumption). That is, Compound A or a salt thereof can also be suitably used as an oxygen consumption enhancer or an active ingredient of an oxygen consumption promoter. The method for calculating oxygen consumption is not particularly limited, and it can be measured, for example, using a commercially available device capable of measuring exhaled gas. Alternatively, oxygen consumption can be evaluated as the cumulative oxygen consumption over a certain period of time. For example, the cumulative oxygen consumption over 24 hours can be calculated from the average oxygen consumption over approximately 24 hours (e.g., 24 hours ± 1 hour) using the following formula: Cumulative oxygen consumption (mL / kg / day) = average VO2 over approximately 24 hours (mL / min) / body weight (kg) × 60 (min / h) × 24 (h) (VO2: oxygen consumption)

[0026] "Increasing oxygen consumption" or "promoting oxygen consumption" refers to increasing oxygen consumption. When compound A or a salt thereof is administered, oxygen consumption over a certain period of time (e.g., 24 hours) can be increased compared to when compound A or a salt thereof is not administered. The increase is preferably 3% or more, more preferably 5% or more, even more preferably 7% or more, and particularly preferably 10% or more. The increase is preferably 20% or less, more preferably 18% or less, and particularly preferably 15% or less. Therefore, the increase can be 3-20%, 5-20%, 7-20%, 10-20%, 3-18%, 5-18%, 7-18%, 10-18%, 3-15%, 5-15%, 7-15%, 10-15%, etc.

[0027] (Lipid Burning Promoters) Compound A or a salt thereof has a lipid burning promoting effect and can therefore be suitably used as an active ingredient of lipid burning promoters. In the present invention, "lipid burning" refers to the metabolism of lipids, particularly fatty acids, derived from diet or fat accumulated in the body in various biological tissues and converted into chemical energy or thermal energy. "Promoting lipid burning" refers to increasing the amount of lipid burned, for example, increasing the cumulative amount of lipid burned over a certain period of time after administration of Compound A. For example, the cumulative amount of lipid burned over 24 hours can be calculated from the average oxygen consumption and average carbon dioxide production over approximately 24 hours (e.g., 24 hours ± 1 hour) using the following formula: Cumulative amount of lipid burned (mg / kg / day) = 1.67 × [average VO2 (mL / min) over approximately 24 hours - average VCO2 (mL / min) over approximately 24 hours] / body weight (kg) × 60 (min / h) × 24 (h) (VO2: oxygen consumption, VCO2: carbon dioxide production)

[0028] When compound A or a salt thereof is administered, the cumulative amount of fat burned over a certain period of time (e.g., 24 hours) can be increased compared to when compound A or a salt thereof is not administered. The increase is preferably 1% or more, more preferably 2% or more, and even more preferably 3% or more. The increase is preferably 10% or less, more preferably 8% or less, and even more preferably 5% or less. Therefore, the increase can be 1-10%, 2-10%, 3-10%, 1-8%, 2-8%, 3-8%, 1-5%, 2-5%, 3-5%, etc.

[0029] The fat burning promoter of the present invention can also be suitably used to promote the burning of fat (particularly white fat) accumulated in the body. That is, Compound A or a salt thereof can also be suitably used as an active ingredient of a fat burning promoter.

[0030] (Thermogenesis Promoting Agent) As described above, Compound A or a salt thereof has an energy consumption-promoting effect, and promoting energy consumption in the body also promotes heat production. Therefore, Compound A or a salt thereof has a thermogenesis-promoting effect and can be suitably used as an active ingredient of a thermogenesis promoter. In the present invention, "thermogenesis" refers to the body generating heat, i.e., energy, due to metabolic activation more than usual. The method for evaluating thermogenesis is not particularly limited, and can be evaluated, for example, by measuring body temperature. The body temperature may be the temperature of any part of the body, such as the rectum, axilla, mouth, or ear. Furthermore, since promoting thermogenesis in the body can increase body temperature, the thermogenesis promoter of the present invention can also be used to increase body temperature. That is, Compound A or a salt thereof can also be suitably used as an active ingredient of a thermogenic agent. The thermogenesis promoter or thermogenic agent of the present invention may be used to prevent or improve hypothermia or body chills (e.g., sensitivity to cold). For example, administration of compound A or a salt thereof can increase rectal temperature after a certain period of time (e.g., 12 weeks of administration twice daily) compared to when compound A or a salt thereof is not administered. The increase is preferably 1% or more, more preferably 2% or more, and even more preferably 3% or more. The increase is preferably 10% or less, more preferably 9% or less, and even more preferably 7% or less. Therefore, the increase can be 1-10%, 2-10%, 3-10%, 1-9%, 2-9%, 3-9%, 1-7%, 2-7%, 3-7%, etc. The increase can be preferably 0.1°C or more, more preferably 0.2°C or more, and even more preferably 0.3°C or more. The increase can be preferably 3°C or less, more preferably 2.8°C or less, and even more preferably 2.5°C or less. Thus, the increase can include an increase of 0.1 to 3°C, 0.2 to 3°C, 0.3 to 3°C, 0.1 to 2.8°C, 0.2 to 2.8°C, 0.3 to 2.8°C, 0.1 to 2.5°C, 0.2 to 2.5°C, 0.3 to 2.5°C, etc.

[0031] (Weight Gain Inhibitor) Compound A or a salt thereof has a weight gain inhibitory effect and can therefore be suitably used as an active ingredient of a weight gain inhibitor. The weight gain inhibitor of the present invention may also be used as a weight-reducing agent. The method for calculating body weight is not particularly limited, and can be calculated, for example, using a commercially available weighing scale or body composition analyzer. For example, if the weight gain over a certain period (e.g., 12 weeks) without administration of compound A or a salt thereof is taken as 100%, the weight gain with administration of compound A or a salt thereof can be 10-90%, 20-90%, 30-90%, 10-80%, 20-80%, 30-80%, 10-70%, 20-70%, 30-70%, etc.

[0032] (Agent for Inhibiting or Reducing Increase in Body Fat Percentage) Compound A or a salt thereof has the effect of inhibiting an increase in body fat percentage or body fat mass (e.g., body fat weight per body weight, particularly white fat weight), and therefore can be suitably used as the active ingredient of an agent for inhibiting an increase in body fat percentage or an agent for reducing body fat percentage, or an agent for inhibiting an increase in body fat mass or an agent for reducing body fat mass. Furthermore, since a decrease in body fat percentage or body fat mass increases lean body mass or lean body weight, and vice versa, the agent for inhibiting or reducing an increase in body fat percentage or an agent for inhibiting or reducing an increase in body fat mass of the present invention can also be suitably used as an agent for inhibiting or increasing a decrease in lean body mass or an agent for inhibiting or increasing a decrease in lean body mass. Furthermore, the agent for inhibiting or reducing an increase in body fat percentage of the present invention can also be suitably used to inhibit an increase in body fat mass, as described above, and further to inhibit the accumulation of body fat. That is, compound A or a salt thereof can also be suitably used as the active ingredient of an agent for inhibiting body fat accumulation.

[0033] "Body fat" refers to fat stored in the body, mostly composed of triglycerides, which are stored primarily in adipocytes. Adipocytes are broadly divided into two types: white adipocytes, such as subcutaneous fat and visceral fat, and brown adipocytes. White adipocytes contain unilocular lipid droplets and store excess energy in the form of triglycerides, which are then broken down into glycerol and free fatty acids as needed and resupplied to the entire body as an energy source. Therefore, in an obese state where energy supply chronically exceeds energy consumption, the lipid droplets stored in white adipocytes become enlarged. The majority of adult adipose tissue is white adipose tissue. White fat (tissue) composed of white adipocytes is not particularly limited, but examples include periepididymal fat, mesenteric fat, perirenal fat, and interscapular fat.

[0034] In the present invention, the method for calculating body fat mass (e.g., white fat weight) is not particularly limited, and can be calculated using, for example, a commercially available body composition analyzer, computed tomography (CT scan), magnetic resonance imaging (MRI), etc. Furthermore, the method for calculating body fat percentage is also not particularly limited, and can be calculated, for example, by the same method as for body fat mass, or can be calculated as the proportion of body fat mass to body weight. Furthermore, when using experimental animals, body fat mass can be calculated by extracting each fat (e.g., white fat) from the body and directly measuring its weight.

[0035] (Muscle-building agent and muscle mass increase promoter) Compound A or a salt thereof can be suitably used as an active ingredient of a muscle-building agent. In the present invention, "muscle-building" refers to enhancing muscle strength and / or increasing muscle mass. Compound A or a salt thereof has the effect of promoting an increase in muscle mass (e.g., muscle weight per body weight, particularly skeletal muscle weight), and therefore can also be used to promote an increase in muscle mass. That is, Compound A or a salt thereof can also be suitably used as an active ingredient of a muscle mass increase promoter. Muscles are not particularly limited, but examples include skeletal muscles, particularly the plantaris muscle, tibialis anterior muscle, and extensor digitorum longus muscle, which are skeletal muscles of the left and right lower limbs. The method for calculating muscle mass (e.g., skeletal muscle weight) is not particularly limited, but can be calculated using, for example, a commercially available body composition analyzer, computed tomography (CT scan), magnetic resonance imaging (MRI), etc. Furthermore, when using experimental animals, muscle mass may be calculated by directly measuring the weight of each muscle (e.g., skeletal muscle) removed from the body. Furthermore, muscle mass may be evaluated, for example, for each of the muscles exemplified above, or by adding up the weights of multiple muscles. The proportion of muscle in body weight can also be referred to as muscle ratio or muscle mass ratio. That is, compound A or a salt thereof can also be used as an active ingredient of an agent for promoting an increase in muscle ratio or muscle mass ratio. Furthermore, since an increase in muscle mass or muscle (mass) ratio also increases (enhances) muscle strength, compound A or a salt thereof can also be suitably used as an active ingredient of a muscle strength-increasing agent or muscle strength-enhancing agent.

[0036] (Agent for preventing or improving obesity) As described above, compound A or a salt thereof has the effects of promoting energy consumption, promoting fat burning, inhibiting an increase in body fat percentage, and inhibiting weight gain, and therefore can be suitably used as an active ingredient of an agent for preventing or improving obesity. "Obesity" refers not only to being overweight, but also to a state in which body fat is excessively accumulated. The degree of obesity can be determined by the international standard index BMI (Body Mass Index) = [weight (kg)] ÷ [height (m)] ２] is used. The standard BMI for both men and women is 22.0, and obesity is defined as "a state in which fat is excessively accumulated in adipose tissue, with a body mass index (BMI) of 25 or more." Compound A or a salt thereof can also be suitably used as an active ingredient of a preventive agent for metabolic syndrome or an agent for improving metabolic syndrome. Metabolic syndrome refers to a combination of obesity, hypertension, dyslipidemia, hyperglycemia (diabetes), etc., and is a condition in which cardiovascular disease is likely to develop. Furthermore, compound A or a salt thereof can also be suitably used as a preventive or therapeutic agent for pathologies or diseases caused by obesity or metabolic syndrome. Diseases caused by obesity or metabolic syndrome are not particularly limited, and examples thereof include arteriosclerosis, heart disease (angina pectoris, myocardial infarction, etc.), stroke, cerebral infarction, etc.

[0037] (Agent for Inhibiting or Reducing Increases in Total Cholesterol) Compound A or a salt thereof has the effect of inhibiting increases in total cholesterol, and can therefore be suitably used as an active ingredient in an agent for inhibiting increases in total cholesterol or a agent for reducing total cholesterol. "Total cholesterol" refers to the total amount of cholesterol measured in blood. High levels of total cholesterol may be considered dyslipidemia, which can lead to various diseases such as arteriosclerosis, myocardial infarction, and cerebral infarction. The method for calculating total cholesterol is not particularly limited, and can be calculated, for example, by collecting blood and measuring the total cholesterol level in the blood. Compound A or a salt thereof can also be suitably used as a preventive or therapeutic agent for pathologies or diseases caused by increases in total cholesterol. Diseases caused by increases in total cholesterol include, but are not limited to, arteriosclerosis, heart disease (angina pectoris, myocardial infarction, etc.), stroke, cerebral infarction, etc.

[0038] (Composition) Compound A or a salt thereof can be used as is, or can be used as a composition by appropriately blending other ingredients within a range that does not impair the effects of the present invention. That is, the present invention can provide a composition containing an energy consumption promoter, a lipid burning promoter, a thermogenesis promoter, a weight gain inhibitor, an agent for inhibiting or reducing an increase in body fat percentage, an agent for promoting muscle mass increase, a muscle-building agent, an agent for preventing or ameliorating obesity, an agent for inhibiting or reducing an increase in total cholesterol level, etc. That is, the composition of the present invention can be suitably used as a composition for promoting energy consumption, promoting lipid burning, promoting thermogenesis, inhibiting weight gain, inhibiting or reducing an increase in body fat percentage, promoting muscle mass increase, muscle-building, preventing or ameliorating obesity, inhibiting or reducing an increase in total cholesterol level, etc. Preferred examples of the composition include food compositions and pharmaceutical compositions. In particular, a food composition is preferred from the viewpoint of daily intake.

[0039] (Food Composition) In the present invention, the food includes a beverage. The form of the food composition in the present invention is not particularly limited as long as it is ingestible by a subject such as a mammal and is suitable for consumption, and examples thereof include solid, liquid, semi-liquid, granular, powder, capsule, cream, paste, etc.

[0040] The food composition of the present invention may contain other ingredients appropriate for the type of food. The other ingredients are not particularly limited as long as they do not impair the effects of the present invention, and examples include various proteins, sugars, fats, trace elements, nutrient-enhancing ingredients, vitamins, and organic acid salts such as citric acid and acetic acid. Furthermore, the food of the present invention may contain additives that are tolerated and commonly used in foods, depending on the type of food, such as sweeteners such as aspartame and stevia, acidulants such as citric acid, malic acid, and tartaric acid, excipients such as dextrin and starch, as well as colorants, flavorings, bittering agents, buffers, thickening agents, gelling agents, stabilizers, gum bases, binders, diluents, emulsifiers, dispersants, suspending agents, antioxidants, preservatives, antiseptics, fungicides, color formers, bleaching agents, brighteners, enzymes, seasonings, and spice extracts.

[0041] In the present invention, the term "food" is used to include health foods, functional foods, foods for specified health uses, nutritional supplements, and foods for the sick. In particular, it is preferable to provide foods suitable for consumers who expect functions such as preventing or improving obesity, i.e., foods for specified health uses. The term "foods for specified health uses" as used herein refers to foods that may be subject to some legal restrictions from a health perspective when they are manufactured or sold for the purpose of preventing or improving obesity.

[0042] The health foods and the like may be in the form of ordinary foods, but are preferably in the form of drinks or supplements (tablets, granules, fine granules, tablets, chewable tablets, capsules (soft capsules, hard capsules), etc.).

[0043] In the present invention, examples of foods to be blended with Compound A or a salt thereof include beverages such as soft drinks, carbonated drinks, nutritional drinks, fruit drinks, and dairy drinks (including concentrated concentrates and powders for adjusting these beverages); carbohydrate-containing foods and drinks such as rice, noodles, bread, and pasta; Western confectioneries such as cookies and cakes, Japanese confectioneries such as buns and yokan, candies, gums, frozen desserts and frozen desserts such as yogurt, pudding, and jelly; processed seafood and livestock foods such as kamaboko, chikuwa, hamburger steak, ham, and sausage; dairy products such as processed milk, fermented milk, yogurt, butter, and cheese; oils and fats and processed oils and fats foods such as margarine, mayonnaise, shortening, whipped cream, and dressing; and seasonings such as sauces and dressings, but are not limited to these.

[0044] (Pharmaceutical Composition) In the present invention, pharmaceuticals include quasi-drugs. The pharmaceutical composition of the present invention may or may not contain suitable additives (e.g., carriers, excipients, diluents, binders, lubricants, disintegrants or disintegration aids, solubilizers, stabilizers, preservatives, antiseptics, bulking agents, thickeners, emulsifiers, dispersants, suspending agents, buffers, etc.) that are pharmaceutically acceptable and selected appropriately depending on the dosage form, and can be prepared and provided in various dosage forms that can be administered orally or parenterally, systemically, or locally, by various known methods.

[0045] The pharmaceutical composition of the present invention can be administered orally or parenterally. When the pharmaceutical composition of the present invention is administered orally, it can be formulated into tablets (including sugar-coated tablets), capsules, granules, powders, pills, oral solutions, suspensions, emulsions, syrups, etc., or can be made into a dry product that is redissolved before use. When the pharmaceutical composition of the present invention is administered parenterally, it can be formulated into injections (e.g., subcutaneous injections, intravenous injections, intramuscular injections, intraperitoneal injections), drip infusions, suppositories (e.g., rectal suppositories, vaginal suppositories), etc., and injectable preparations are provided in unit-dose ampoules or multi-dose containers.

[0046] Here, formulations can be prepared, for example, as follows. Oral preparations can be prepared by adding excipients (e.g., lactose, sucrose, starch, mannitol), disintegrants (e.g., calcium carbonate, carboxymethylcellulose calcium), binders (e.g., pregelatinized starch, gum arabic, carboxymethylcellulose, polyvinylpyrrolidone, hydroxypropylcellulose), and lubricants (e.g., talc, magnesium stearate, polyethylene glycol 6000) to the active ingredient, compressing the mixture, and then coating the mixture by a method known per se, if necessary, for taste masking, enteric coating, or sustained release. Examples of coating agents that can be used include ethyl cellulose, hydroxymethyl cellulose, polyoxyethylene glycol, cellulose acetate phthalate, hydroxypropyl methylcellulose phthalate, and Eudragit (manufactured by Rohm, Germany, methacrylic acid / acrylic acid copolymer).

[0047] (Content in Composition) In the above-mentioned food composition, pharmaceutical composition, or other composition, the content of Compound A or a salt thereof is, for example, 0.01% by mass or more, 0.1% by mass or more, 1.0% by mass or more, 95% by mass or less, 80% by mass or less, 60% by mass or less, etc., of the total mass of the composition. Further examples include 0.01 to 95% by mass, 0.1 to 80% by mass, 1.0 to 60% by mass, etc.

[0048] In the present invention, the dose of Compound A or a salt thereof, which is an active ingredient, is not particularly limited as long as it does not impair the effects of the present invention, but is, for example, in the range of 0.6 mg to 36,000 mg / day, preferably 30 mg to 720 mg / day (for adults), and most preferably 60 to 360 mg / day (for adults). However, the dose may be appropriately determined depending on the age (months), body weight, sex, symptoms, sensitivity to Compound A or a salt thereof, etc. of the subject to be administered.

[0049] (Administration Method) The administration method of the agent or composition of the present invention containing Compound A or a salt thereof is not particularly limited as long as it does not impair the effects of the present invention, and examples thereof include a period of 1 day or more, 3 days or more, 5 days or more, 1 week or more, 2 weeks or more, 3 weeks or more, 4 weeks or more, 5 weeks or more, 6 weeks or more, 7 weeks or more, preferably 8 weeks or more, 9 weeks or more, more preferably 10 weeks or more, 11 weeks or more, and even more preferably 12 weeks or more. Higher effects can be obtained by continuous administration over a long period of time. Furthermore, the number of administrations per day is not particularly limited, and may be administered once a day, or in multiple doses, such as two or three or more times a day.

[0050] (Subject to be administered) The subject to be administered with the agent or composition of the present invention containing Compound A or a salt thereof is not particularly limited as long as it is an animal that needs or desires it, and examples thereof include mammals such as humans, pigs, cows, horses, goats, sheep, wild boars, rabbits, mice, rats, hamsters, guinea pigs, monkeys, rhesus monkeys, cynomolgus monkeys, marmosets, orangutans, chimpanzees, dogs, and cats, with humans being preferred.

[0051] (Combination Use) The agent or composition of the present invention may further contain one or more active ingredients other than Compound A or a salt thereof. Furthermore, when administering the composition of the present invention, it may be administered in combination with one or more active ingredients other than Compound A or a salt thereof, or an agent containing them.

[0052] (Use) The agent or composition of the present invention can be used for promoting energy consumption, increasing oxygen consumption, promoting lipid burning, promoting fat burning, promoting thermogenesis, increasing body temperature, suppressing weight gain, suppressing or reducing an increase in body fat percentage, suppressing or reducing an increase in body fat mass, suppressing body fat accumulation, promoting an increase in muscle mass, building muscle, preventing or ameliorating obesity, and / or suppressing or reducing an increase in total cholesterol. Here, the use may be either therapeutic or non-therapeutic. "Non-therapeutic" is a concept that does not include medical procedures, i.e., a concept that does not include methods of surgery, treatment, or diagnosis on humans, and more specifically, a concept that does not include methods of surgery, treatment, or diagnosis performed on humans by a physician or a person under the direction of a physician.

[0053] The present invention will be explained in more detail below with reference to examples, but the technical scope of the present invention is not limited to these examples.

[0054] 1. Test materials and experimental methods 1-1. Test materials (1) Test substance Name: Compound A (a compound represented by the following formula (A)) Manufacturing method: Crystalline Compound A (stereostructure is a mixture of SS and RR isomers in the RS representation method) was manufactured according to the method described in paragraphs

[0048] -

[0049] of WO2018 / 199040. Appearance: Powder, white Storage conditions: Refrigerated Usage method: A predetermined weight was weighed out and dispersed in a 0.5% carboxymethylcellulose (CMC) solution as a solvent to prepare an oral administration solution.

[0055] (2) Control substance Name: CMC Manufacturer: Nacalai Tesque, Inc. Container: 500 mL plastic bottle Lot number: M0A9874 Appearance: White powder Storage conditions: Refrigerated Method of use: A specified weight was weighed out and dissolved in Otsuka distilled water to a concentration of 0.5% to prepare a solution for oral administration.

[0056] 1-2. Animals Used (1) Species, Strain, and Sex: Mouse, C57BL / 6J, Male (2) Reason for Selecting Species and Strain: Mice are widely used in safety testing and pharmacological testing of pharmaceuticals and medical devices, and the strain of mice used in this test was selected because of its well-known characteristics. (3) Microbial Control: SPF (4) Producer: Jackson Laboratory Japan, Inc. (5) Number of Animals Arrived: 48 (6) Age at Arrival: 7-8 weeks (7) Weight at Arrival: 21-28g (8) Individual Identification: Numbers were assigned to the tail with permanent marker. In this test, each animal was assigned a number from 1 to 40. (9) Quarantine and Acclimatization: No quarantine was performed. After arrival, an acclimation period was set up, during which the animals were kept in a breeding room on a solid, ultra-high-fat diet (D12492), and their health was monitored at all times.

[0057] 1-3. Breeding environment Temperature: 23±3°C Humidity: 55±15% Ventilation rate: 13-16 times / hour Lighting time: 12 hours (7:00-19:00)

[0058] 1-4. Feed During the test period, the animals were given free access to an ultra-high fat feed, D12492 (EP Trading Co., Ltd., Lot: 22041308). After the test was completed, all of the test food fed to the animals was discarded. Name: D12492 (ultra-high fat feed, 60 kcal% fat, blue) Manufacturer: EP Trading Co., Ltd. Lot number: 22041308 Method of use: Removed from the refrigerator when feeding. Composition: See Table 1.

[0059]

[0060] 1-5. Drinking water Tap water was provided ad libitum from a water bottle.

[0061] 1-6. Group composition The composition is shown in Table 2. On the day of grouping, animals that showed no abnormalities were weighed, and the animals were randomly assigned to groups stratified by weight using the statistical analysis system EXSUS Ver. 10 (EP Clore Co., Ltd.).

[0062]

[0063] 1-7. Preparation and administration of test substance (1) Method for preparing test substance Compound A was weighed and crushed uniformly in a magnetic mortar with the addition of a small amount of 0.5% CMC. 0.5% CMC was further added to the crushed Compound A to adjust the concentration to 720 mg / 10 mL. After preparation, the solution was stored in a refrigerator. (2) Method for administering test substance The test substance was orally administered (10 mL / kg) using an oral probe twice a day, once in the morning and once in the afternoon, for 12 weeks. During oral administration, the test substance was administered manually.

[0064] 1-8. Observations (1) General Observation: The animals' general condition was closely monitored throughout the administration period of the test substance. (2) Calculation of Calorie Intake: Food intake (g) was measured at least once a week from the day of grouping until necropsy. Calorie intake was calculated for each animal by multiplying the food intake by the calorie content (kcal) per weight. (3) Exhaled Gas Analysis: Exhaled gas was measured using a 32-channel small animal energy metabolism measurement system (ARCO-2000-RAT, Arco Systems, Inc.). The animals' oxygen consumption (mL / min) and carbon dioxide production (mL / min) were measured at 10-minute intervals at an airflow rate of 0.3 L / min. Measurements were continued for approximately 24 hours after the end of oral administration in the morning of the day before necropsy. Cumulative 24-hour oxygen consumption (mL / kg / day), energy expenditure (kcal / kg / day), and lipid combustion (mg / kg / day) were calculated using the following formulas. Calculation formula: Cumulative oxygen consumption (mL / kg / day) = average VO2 over approximately 24 hours (mL / min) / body weight (kg) x 60 (min / h) x 24 (h) Cumulative energy expenditure (kcal / kg / day) = [{3.816 x average VO2 over approximately 24 hours (mL / min) + 1.231 x average VCO2 over approximately 24 hours (mL / min)} / body weight (kg) x 60 (min / h) x 24 (h)] / 1000 (cal / kcal) Cumulative fat burned (mg / kg / day) = 1.67 x [average VO2 over approximately 24 hours (mL / min) - average VCO2 over approximately 24 hours (mL / min)] / body weight (kg) x 60 (min / h) x 24 (h) (VO2: oxygen consumption, VCO2: carbon dioxide production) (4) Rectal temperature Before necropsy, a small animal body temperature controller (NS-TC10 Temperature Controller, Neuroscience Inc.) connected to a rectal temperature measurement probe was inserted into the rectum to measure rectal temperature. (5) Body weight measurement This was done at the time of arrival and every week from the day of group allocation until necropsy. It was also done on the day of body composition measurement and just before necropsy. (6) Body composition Body fat mass and lean body mass were measured using a body composition analyzer (EchoMRI-700, Hitachi, Ltd.) at 6, 9, and 12 weeks after test diet intake, and body fat percentage and lean body mass percentage were calculated by dividing by body weight.

[0065] 1-9. Test Methods After arrival, animals were fed an ultra-high-fat solid diet (D12492) ad libitum. After the acclimation period, animals were divided into groups based on body weight. Subsequently, animals were individually housed and fed the ultra-high-fat diet ad libitum. All groups were orally administered the test substance twice daily (once in the morning and once in the afternoon) (CON group: oral administration of 0.5% CMC, Compound A group: oral administration of Compound A). The first administration day was counted as day 0 of the study. Five animals per group were designated as the first half animals, and the remaining animals were designated as the second half animals. Feeding and administration of the second half animals began on day 2 of the first half animals (day 0 of the study for the second half animals). To acclimate the animals to the environment in the breath gas measurement chamber, after oral administration in the morning (9:00 AM) on days 7, 21, and 49 of the study, the animals were individually housed in the breath gas measurement chamber for 5.5 hours (10:00 AM - 3:30 PM) with free access to water and fasting, with free access to water. On days 28 and 65, after oral administration in the morning (11:00 AM), all animals were promptly placed individually in a breath-gas measuring chamber and allowed to acclimate for approximately 24 hours with free access to water and food. Oral administration was performed in the afternoon (15:30 AM) of the same day and the morning (8:30 AM) of the following day. After administration, the animals were promptly placed back in the breath-gas measuring chamber. After acclimatization, the animals were returned to their cages. On day 82, all animals were promptly placed in the breath-gas measuring chamber before the morning oral administration (10:00 AM). Oral administration was performed in the morning (11:00 AM) and afternoon (15:30 PM) of the same day. After oral administration in the morning (8:30 AM) of the following day, breath-gas measurements were performed until necropsy. On day 83, animals were subjected to necropsy in the afternoon (13:00 PM). At necropsy, the animals underwent laparotomy under isoflurane anesthesia, and blood was collected from the caudal vena cava. After blood collection, the animals were euthanized by exsanguination from the blood collection site, and organs (fat, skeletal muscle) were collected.

[0066] 1-10. Sample Collection (1) White Adipose Tissue 1: Peri-epididymal Fat At autopsy, the fat surrounding the left and right epididymis was removed, followed by the removal of the epididymis. After lightly flushing with saline (0.9% sodium chloride aqueous solution, manufactured by Otsuka Pharmaceutical Factory, Inc.) and wiping off the moisture, the left and right tissues were weighed together using a precision balance. The right tissue was frozen in liquid nitrogen and then stored frozen in a freezer set at -80°C until analysis. The left organ was stored in 10% neutral buffered formalin until analysis.

[0067] (2) White adipose tissue 2: mesenteric fat. At autopsy, fat tissue was removed from the stomach to the rectum. It was lightly flushed with saline (0.9% sodium chloride aqueous solution, manufactured by Otsuka Pharmaceutical Factory, Inc.), wiped dry, and then weighed using a precision balance. It was frozen in liquid nitrogen and then stored frozen in a freezer set at −80°C until analysis.

[0068] (3) White adipose tissue 3: Perirenal fat At autopsy, the fat tissue surrounding the left and right kidneys was removed, lightly flushed with saline (0.9% sodium chloride aqueous solution, manufactured by Otsuka Pharmaceutical Factory, Inc.), wiped dry, and then weighed on a precision balance. The tissue was frozen in liquid nitrogen and then stored frozen in a freezer set at -80°C until analysis.

[0069] (4) White adipose tissue 4: interscapular white fat At autopsy, the white adipose tissue surrounding the interscapular brown adipose tissue was removed, lightly flushed with saline (0.9% sodium chloride solution, Otsuka Pharmaceutical Factory, Inc.), wiped dry, and weighed using a precision balance. It was then frozen in liquid nitrogen and stored frozen in a freezer set at −80°C until analysis.

[0070] (5) Skeletal Muscles The left and right lower limb skeletal muscles, i.e., the plantaris, tibialis anterior, and extensor digitorum longus, were collected at autopsy and weighed using a precision balance. They were then frozen in liquid nitrogen and stored in a freezer set at −80°C until analysis.

[0071] (6) Blood. At autopsy, abdominal incision was performed under isoflurane anesthesia, and approximately 0.5 mL of blood was collected from the caudal vena cava and placed in heparin-containing plasma collection tubes (BD Microtainer PST™ Tubes with Lithium Heparin 365985 (yellow-green); Becton, Dickinson, and Co., Japan) and temporarily stored on ice. After centrifugation (3,000 rpm, 10 min, 4°C), the supernatant plasma was transferred to a 1.5 mL microtube (1.5 mL Hypermicrotube, round bottom, hard touch 131-715C, WATSON) and frozen in a freezer set at −80°C until analysis. Total cholesterol in plasma was measured by the Nagahama Life Science Laboratory, Nagahama Office, Oriental Yeast Co., Ltd.

[0072] 1-11. Data collection and statistical analysis Data are expressed as mean ± standard deviation. For statistical processing, a two-sample equal variance t-test (two-tailed test) was performed, and intergroup comparisons were made using the CON group as a control. In both cases, the significance level was set at 5%. Excel (Microsoft 2013 version) was used for these analyses.

[0073] 2. Results 2-1. Calorie intake There was no difference between the groups in the average daily calorie intake during the test period (Table 3, Figure 1). One animal in the CON group had missing data due to incomplete measurement, so the relevant part (food intake on days 4 and 5) was omitted from the data.

[0074]

[0075] 2-2. Oxygen consumption, energy consumption, and amount of fat burned The compound A administration group had significantly higher cumulative values ​​of oxygen consumption, energy consumption, and amount of fat burned over 24 hours (11:32-11:32) from the start of administration to the end of measurement compared to the CON group (Table 4, Figures 2 to 5). These results demonstrate that compound A has the effect of increasing oxygen consumption, energy consumption, and amount of fat burned.

[0076]

[0077] 2-3. Rectal temperature Rectal temperature was significantly higher in the Compound A administration group compared to the CON group (Table 5, Figure 6). These results indicate that ingestion of Compound A promoted heat production in the mice and elevated their body temperature. In other words, Compound A was shown to have the effects of promoting heat production and elevating body temperature.

[0078]

[0079] 2-4. Body Weight Regarding the change in body weight during the administration period of the test diet, the Compound A administration group tended to have lower body weights at 7, 8, and 9 weeks after the start of the study compared to the CON group, and significantly lower values ​​were observed at 10, 11, and 12 weeks (Table 6, Figure 7). These results demonstrated that Compound A has the effect of suppressing body weight gain. For example, after 12 weeks of administration, the CON group gained an average of 7.2 g in body weight, while the Compound A administration group gained an average of 3.8 g. In other words, when the weight gain of the CON group was taken as 100%, the weight gain of the Compound A administration group was 52.8 ((3.8 ÷ 7.2) × 100)%.

[0080]

[0081] 2-5. Body fat percentage and lean body mass percentage Regarding body fat percentage and lean body mass percentage, the compound A administration group tended to have lower body fat percentage and higher lean body mass percentage compared to the CON group at 6 weeks of test diet intake, and at 9 and 12 weeks, the compound A administration group had significantly lower body fat percentage and higher lean body mass percentage (Table 7, Figure 8). These results indicated that compound A has the effect of suppressing an increase in body fat percentage (i.e., the effect of suppressing a decrease in lean body mass percentage).

[0082]

[0083] 2-6. White Fat Weight The white fat weight per body weight in the compound A group was significantly lower than that in the CON group in perididymal fat, mesenteric fat, perirenal fat, and interscapular fat (Table 8, Figure 9). These results indicate that compound A has the effect of suppressing the increase in white fat weight per body weight.

[0084]

[0085] 2-7. Muscle Weight Regarding weight per body weight, the weights of the plantaris, tibialis anterior, and extensor digitorum longus muscles, as well as the total weight of these three muscles, were significantly higher in the Compound A administration group (Table 9, Figure 10). These results indicated that Compound A has the effect of promoting an increase in muscle weight per body weight.

[0086]

[0087] 2-8. Total cholesterol level The Compound A administration group showed significantly lower plasma total cholesterol levels than the CON group (Table 10, Figure 11). These results indicated that Compound A has the effect of suppressing an increase in total cholesterol levels.

[0088]

[0089] The present invention can be particularly effectively used in the fields of food and pharmaceutical production.

Claims

1. An energy consumption promoter comprising a compound represented by the following formula (A) or a salt thereof as an active ingredient:

2. The energy consumption promoter according to claim 1, which promotes energy consumption by increasing oxygen consumption.

3. A lipid burning promoter comprising, as an active ingredient, a compound represented by the following formula (A) or a salt thereof:

4. The lipid burning promoter according to claim 3 for promoting lipid burning.

5. A heat production promoter comprising, as an active ingredient, a compound represented by the following formula (A) or a salt thereof:

6. The heat production promoter according to claim 5 for increasing body temperature.

7. A weight gain inhibitor comprising a compound represented by the following formula (A) or a salt thereof as an active ingredient:

8. An agent for suppressing or reducing an increase in body fat percentage, comprising a compound represented by the following formula (A) or a salt thereof as an active ingredient:

9. An agent for suppressing or reducing an increase in body fat percentage according to claim 8, for suppressing an increase in body fat mass.

10. An agent for suppressing or reducing an increase in body fat percentage according to claim 8, for suppressing accumulation of body fat.

11. A muscle-building agent comprising, as an active ingredient, a compound represented by the following formula (A) or a salt thereof:

12. The muscle-building agent according to claim 11 for promoting an increase in muscle mass.

13. An agent for preventing or ameliorating obesity, comprising a compound represented by the following formula (A) or a salt thereof as an active ingredient:

14. An agent for suppressing an increase in or reducing total cholesterol amount, comprising a compound represented by the following formula (A) or a salt thereof as an active ingredient:

15. A pharmaceutical composition or food composition comprising the agent according to any one of claims 1 to 14.