Muscle atrophy inhibitor

Abstract

As one embodiment, the present application discloses a muscle atrophy inhibitor that includes a long-chain hydroxylated fatty acid as an active ingredient.

Description

Muscle atrophy inhibitors

[0001] The present invention relates to a long-chain hydroxylated fatty acid that inhibits muscle atrophy, and is useful in the fields of medicine, food, etc.

[0002] In humans and animals, muscle mass decreases from middle age onward with aging and lifestyle changes. As people age, sarcopenia, a type of muscle atrophy caused by aging, becomes a problem. In addition to sarcopenia, other muscle atrophy causes include disuse muscle atrophy, which occurs due to immobility such as being immobilized in a cast or being bedridden, and myopathy, a neuromuscular disease, which inhibits independent activity. When muscle atrophy inhibits independent activity, it affects daily life and is a major social problem.

[0003] 3-Hydroxyisovaleric acid is known to help maintain muscle mass, and a composition containing 3-hydroxyisovaleric acid and an amino sugar has been reported to enhance its unique flavor and its ability to prevent muscle atrophy (Patent Document 1). Other reports include the use of kynurenic acid, a tryptophan metabolite, in the treatment and prevention of muscle atrophy-related diseases (Patent Document 2), and a muscle atrophy-inhibiting composition containing a tripeptide as an active ingredient (Patent Document 3). Gene expression regulators containing odd-numbered fatty acids as active ingredients have also been reported to inhibit muscle atrophy by suppressing metallothionein-2 gene expression and enhancing nucleoporin-210 gene expression (Patent Document 4). Muscle atrophy has also been reported to be inhibited by suppressing the expression of the chemokine CXCL10 using a neutralizing antibody (Patent Document 5).

[0004] Non-Patent Document 1 discusses nutrients involved in muscle synthesis, noting that omega-3 fatty acids contribute to promoting muscle synthesis, while omega-6 fatty acids promote muscle protein breakdown and inhibit muscle hypertrophy. Non-Patent Document 2, which conducted a statistical analysis to identify data summarizing sarcopenia disease and the intake of omega-3 and omega-6 fatty acids, reported a negative correlation between omega-3 fatty acid intake and the incidence of sarcopenia, and reported a relationship between omega-3 fatty acid intake and sarcopenia. Non-Patent Document 3 also considers sarcopenia to be an inflammatory disease, and claims that the anti-inflammatory effects of omega-3 fatty acids could be used to treat sarcopenia, but there are many unknowns regarding their effectiveness. As mentioned above, there are reports that 3-hydroxyisovaleric acid, amino acid metabolites, and peptides have muscle atrophy-inhibiting effects, and reports suggesting the effects of omega-3 fatty acids on sarcopenia, but there have been no reports to date of long-chain hydroxylated fatty acids inhibiting muscle atrophy.

[0005] JP 2016-88844 JP 2019-530743 WO2018 / 105550 JP 2019-172614 JP 2022-162858

[0006] Darren G. et al., Biogerontology (2012) 13:345-358Yi Zhang et al., Frontiers in Nutrition, January 2022, Volume 8, Article 738083Ahmed Al Saedi et al., Bone 164 (2022) 116539

[0007] The object of the present invention is to provide functional fatty acids for suppressing muscle atrophy, and to provide, as embodiments thereof, drugs and methods for improving health conditions by suppressing muscle atrophy caused by immobilization in a cast, aging, intake of a high-fat diet, metabolic disorders, neurological diseases, cancer, etc.

[0008] In light of the above-mentioned problems, the present inventors have conducted extensive research and discovered that administration of long-chain hydroxylated fatty acids suppresses muscle atrophy in hindlimb-immobilized mice, a representative model of muscle atrophy. Furthermore, they have also discovered that administration of long-chain hydroxylated fatty acids suppresses muscle atrophy induced in mice fed a high-fat diet. Furthermore, they have found that administration of a hydroxylated fatty acid with 18 carbon atoms and a hydroxyl group at the 10th position is highly effective in suppressing muscle atrophy, leading to the completion of the present invention.

[0009] That is, the present invention provides the following specific embodiments, although the present invention is not limited to these. [1] A muscle atrophy inhibitor comprising a long-chain hydroxylated fatty acid as an active ingredient. [2] The muscle atrophy inhibitor according to [1], wherein the long-chain hydroxylated fatty acid has 18 carbon atoms. [3] The muscle atrophy inhibitor according to [2], wherein the long-chain hydroxylated fatty acid has a hydroxyl group at position 10. [4] The muscle atrophy inhibitor according to [3], wherein the long-chain hydroxylated fatty acid having a hydroxyl group at position 10 is 10-hydroxy-cis-12-octadecenoic acid. [5] The muscle atrophy inhibitor according to any of [1] to [4], which is used to prevent or treat a disease accompanied by muscle atrophy. [6] The muscle atrophy inhibitor according to any of [1] to [5], which is used to improve muscle mass loss. [7] The muscle atrophy inhibitor according to [6], wherein the muscle mass loss is due to a decrease in activity caused by immobilization or the intake of a high-fat diet. [8] The muscle atrophy inhibitor according to [5], wherein the disease is sarcopenia, disuse muscle atrophy, muscle atrophy due to obesity, muscle atrophy due to diabetes, myopathy, cachexia, metabolic disorders, neurological (neurological) diseases, or cancer. [9] The muscle atrophy inhibitor according to [8], wherein the myopathy is muscular dystrophy, distal myopathy, congenital myopathy, glycogen storage disease, mitochondrial myopathy, steroid myopathy, alcoholic myopathy, rhabdomyolysis, or myasthenia gravis.

[10] The muscle atrophy inhibitor according to any one of [1] to [9], which is a pharmaceutical product (particularly for human use).

[11] A composition for improving muscle mass loss, comprising a long-chain hydroxylated fatty acid.

[12] The composition according to

[11] , wherein the long-chain hydroxylated fatty acid has 18 carbon atoms.

[13] The composition according to

[12] , wherein the long-chain hydroxylated fatty acid has a hydroxyl group at the 10-position.

[14] The composition according to

[13] , wherein the long-chain hydroxylated fatty acid having a hydroxyl group at position 10 is 10-hydroxy-cis-12-octadecenoic acid.

[15] The composition according to any one of

[11] to

[14] , wherein the loss of muscle mass is due to a decrease in activity caused by immobilization or a loss of muscle mass associated with the intake of a high-fat diet.

[16] The composition according to any one of

[11] to

[14] , wherein the loss of muscle mass is due to a metabolic disorder, neurological (neurological disease), or cancer.

[17] The composition according to any one of

[11] to

[14] , wherein the composition is a pharmaceutical product.

[18] The composition according to any one of

[11] to

[14] , wherein the composition is a food or a food additive.

[19] The composition according to any one of

[11] to

[14] , which is a feed or a feed additive.

[0010]

[20] A method for inhibiting muscle atrophy in a human or animal, comprising administering an effective amount of a long-chain hydroxylated fatty acid to a subject in need thereof.

[21] A long-chain hydroxylated fatty acid used for inhibiting muscle atrophy.

[22] Use of a long-chain hydroxylated fatty acid for the manufacture of a drug for inhibiting muscle atrophy.

[0011] In one embodiment, the present invention provides a muscle atrophy inhibitor, a composition for improving muscle mass loss, etc., which contain a long-chain hydroxylated fatty acid as an active ingredient. The composition, etc., is a composition that inhibits muscle atrophy, which is a loss of muscle caused by factors such as a decrease in activity due to immobility caused by aging or cast immobilization, eating habits such as high-fat intake, metabolic disorders, neurological (neurological diseases), and cancer, and can be used in a variety of fields, including pharmaceuticals, foods, and feeds.

[0012] The figures show the food intake of mice fed a normal diet, a linoleic acid-mixed diet (LA), and a 10-hydroxy-cis-12-octadecenoic acid-mixed diet (HYA) (Example 1, described below). The figures show the soleus muscle weights of mice fed a normal diet, a linoleic acid-mixed diet (LA), and a 10-hydroxy-cis-12-octadecenoic acid-mixed diet (HYA) 20 days later (including the last 10 days of immobilization treatment) (Example 1, described below). The figures show the gastrocnemius muscle weights of mice fed a normal diet, a linoleic acid-mixed diet (LA), and a 10-hydroxy-cis-12-octadecenoic acid-mixed diet (HYA) 20 days later (including the last 10 days of immobilization treatment) (Example 1, described below). The cross-sectional area of ​​muscle fibers was measured when the soleus muscle was cut at its maximum diameter cross section after 20 days (including the last 10 days of immobilization treatment) of mice fed a normal diet, a linoleic acid-containing diet (LA), or a 10-hydroxy-cis-12-octadecenoic acid-containing diet (HYA) (see Example 1 below). The body weights of mice fed a normal diet, a high-fat diet, a 10-hydroxy-cis-12-octadecenoic acid-added high-fat diet (HYA), or a linoleic acid-added high-fat diet (LA) after 14 days (see Example 2 below). The AUC (area under the curve) of blood glucose levels after 14 days of mice fed a normal diet, a high-fat diet, a 10-hydroxy-cis-12-octadecenoic acid-added high-fat diet (HYA), or a linoleic acid-added high-fat diet (LA) (see Example 2 below) (see Example 2 below). Figure 1 shows the muscle weights of the soleus muscle after 14 days when mice were fed a normal diet, a high-fat diet, a high-fat diet supplemented with 10-hydroxy-cis-12-octadecenoic acid (HYA), or a high-fat diet supplemented with linoleic acid (LA) (see Example 2 below). Figure 1 shows the muscle weights of the gastrocnemius muscle after 14 days when mice were fed a normal diet, a high-fat diet, a high-fat diet supplemented with 10-hydroxy-cis-12-octadecenoic acid (HYA), or a high-fat diet supplemented with linoleic acid (LA) (see Example 2 below). Figure 1 shows the results of HE staining of the sections (Figure (A)) and a comparison of the cross-sectional area of ​​the tibialis anterior muscle after 14 days when mice were fed a normal diet, a high-fat diet, a high-fat diet supplemented with 10-hydroxy-cis-12-octadecenoic acid (HYA), or a high-fat diet supplemented with linoleic acid (LA) (see Example 2 below).

[0013] The present invention is now described in detail. Unless otherwise defined in the context, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, the preferred methods and materials are described below. The contents of all publications mentioned herein, including patents and patent applications, are incorporated herein by reference to the same extent as if fully set forth.

[0014] The present invention provides muscle atrophy inhibitors, compositions for improving muscle mass loss, etc., which contain long-chain hydroxylated fatty acids. Examples of long-chain hydroxylated fatty acids include fatty acids having 16 to 22 carbon atoms, with fatty acids having 18 carbon atoms being preferred. The hydroxylated fatty acids are preferably hydroxylated fatty acids having a hydroxyl group at the 10-position.

[0015] More specifically, the long-chain hydroxylated fatty acids of the present invention include, but are not limited to, 10-hydroxy-cis-12-octadecenoic acid (hereinafter also referred to as HYA), 10-hydroxy-cis-12,cis-15-octadecadienoic acid (hereinafter also referred to as αHYA), 10-hydroxy-cis-6,cis-12-octadecadienoic acid (hereinafter also referred to as γHYA), 10,12-dihydroxyoctadecanoic acid (hereinafter also referred to as rHYA), 10-hydroxyoctadecanoic acid (hereinafter also referred to as HYB), and 10-hydroxyoctadecanoic acid (hereinafter also referred to as HYB). 10-hydroxy-cis-15-octadecenoic acid (hereinafter also referred to as αHYB), 10-hydroxy-cis-6-octadecenoic acid (hereinafter also referred to as γHYB), 10-hydroxy-trans-11-octadecenoic acid (hereinafter also referred to as HYC), 10-hydroxy-trans-11,cis-15-octadecadienoic acid (hereinafter also referred to as αHYC), 10-hydroxy-cis-6,trans-11-octadecadienoic acid (hereinafter also referred to as γHYC), 10-hydroxy -cis-6,trans-11,cis-15-octadecatrienoic acid (hereinafter also referred to as sHYC), 10,13-dihydroxy-octadecanoic acid (hereinafter also referred to as HYE), 10,13-dihydroxy-cis-15-octadecenoic acid (hereinafter also referred to as αHYE), 10,13-dihydroxy-cis-6-octadecenoic acid (hereinafter also referred to as γHYE), 13-hydroxy-cis-9-octadecenoic acid (hereinafter also referred to as HYD), 13-hydroxy-cis-9,cis-15-octadecenoic acid Examples of the hydroxybenzoic acid include 13-hydroxy-cis-6,cis-9-octadecadienoic acid (hereinafter also referred to as αHYD), 13-hydroxy-cis-6,cis-9,cis-15-octadecatrienoic acid (hereinafter also referred to as sHYD), 13-hydroxy-cis-5,cis-9-octadecadienoic acid, and 13-hydroxy-trans-5,cis-9-octadecadienoic acid, and preferably 10-hydroxy-cis-12-octadecenoic acid.

[0016] The long-chain hydroxylated fatty acids of the present invention can be prepared by known means, and production methods are described, for example, in WO2013 / 168310 and WO2015 / 111699. 10-Hydroxy-cis-12-octadecenoic acid can be prepared with reference to Biochemical and Biophysical Research Communications 416 (2011) pp. 188-193, etc.

[0017] The muscle atrophy inhibitors and compositions for improving muscle mass loss containing long-chain hydroxylated fatty acids according to embodiments of the present invention are used to prevent or treat muscle atrophy, but the causes of muscle atrophy are not limited. Possible causes of muscle atrophy include cast immobilization due to fractures or the like, decreased physical activity due to hospitalization or aging, eating habits such as high-fat diets, obesity, metabolic disorders, neurological diseases (neurological), and cancer. Examples of diseases that cause muscle atrophy include disuse muscle atrophy, sarcopenia, muscle atrophy due to obesity, muscle atrophy due to diabetes, myopathy, and cachexia.

[0018] The long-chain hydroxylated fatty acids can be used alone or in the form of a composition formulated as described below (hereinafter collectively referred to as the "composition of the present invention"). The composition of the present invention can be used, for example, as a pharmaceutical, food, feed, etc., or by being incorporated therein. When using the composition of the present invention, it may be used in combination with other pharmaceuticals, etc., if necessary.

[0019] When the composition of the present invention is used as a pharmaceutical, the pharmaceutical may be in the form of a powder, granules, pills, soft capsules, hard capsules, tablets, chewable tablets, rapidly disintegrating tablets, syrup, liquid, suspension, etc. These preparations are prepared according to conventional methods.

[0020] Examples of additives that can be used for formulation include animal and vegetable oils such as soybean oil, safflower oil, olive oil, germ oil, sunflower oil, beef tallow, and sardine oil; polyhydric alcohols such as polyethylene glycol, propylene glycol, glycerin, and sorbitol; surfactants such as sorbitan fatty acid esters, sucrose fatty acid esters, glycerin fatty acid esters, and polyglycerin fatty acid esters; excipients such as purified water, lactose, starch, crystalline cellulose, D-mannitol, lecithin, gum arabic, sorbitol solution, and sugar solution; sweeteners, coloring agents, pH adjusters, and flavorings. Liquid formulations may be dissolved or suspended in water or other suitable medium at the time of administration. Tablets and granules may be coated by well-known methods.

[0021] If oral administration is difficult, the drug may be administered as enteral nutrition, or through a nasogastric tube, gastrostomy tube, or enterostomy tube.

[0022] The composition of the present invention can be used as a food or food additive. Examples of foods include, but are not limited to, general foods, health foods, functional foods, nutritional supplements, health-related foods (e.g., foods for specified health uses, foods with functional claims, and foods with nutrient functions), and special-purpose foods (e.g., foods for infants, foods for pregnant women, and foods for the sick). The composition of the present invention may also be provided or sold as a food labeled with uses related to the inhibition of muscle atrophy, the inhibition of muscle mass loss, and muscle maintenance. Such "labeling" includes all acts intended to inform consumers of the uses. As long as the expression can evoke or infer the uses, it all falls under the category of "labeling" in this embodiment, regardless of the purpose of the labeling, the content of the labeling, the object or medium on which it is displayed, etc.

[0023] The labeling is not particularly limited, but is preferably, for example, labeling that claims to inhibit muscle atrophy, inhibit the decrease in muscle mass, and maintain muscle, and more preferably labeling as a food that has been approved or notified as necessary (health functional foods such as foods for specified health uses, foods with functional claims, and foods with nutrient function claims, foods for special dietary uses, etc.). Examples of labeling include "has the function of inhibiting muscle atrophy," "has the function of inhibiting the decrease in muscle mass," "has the function of inhibiting the decrease in muscle strength," "has the function of inhibiting muscle wasting," "has the function of supporting the maintenance of muscle mass and muscle strength," "has the function of improving walking ability," and "has the function of maintaining walking ability." Foods that have been approved or notified for functional claims can be distinguished from general foods.

[0024] When the composition of the present invention is used as a food or food additive, the food may be in any form that can be orally ingested, such as a solution, suspension, powder, or solid molding, and is not particularly limited. Specific examples include supplements (powders, granules, soft capsules, hard capsules, tablets, chewable tablets, rapid-disintegrating tablets, syrups, liquids, etc.), beverages (carbonated drinks, lactic acid drinks, sports drinks, fruit juice drinks, vegetable drinks, soy milk drinks, coffee drinks, tea drinks, powdered drinks, concentrated drinks, nutritional drinks, alcoholic drinks, etc.), sweets (gummy candies, jellies, gum, chocolate, cookies, candy, caramel, Japanese sweets, snacks, etc.), instant foods (instant noodles, retort foods, canned foods, microwave foods, instant soups / miso soups, freeze-dried foods, etc.), oils and fatty foods (mayonnaise, dressings, butter, cream, margarine, etc.), flour products (bread, pasta, noodles, cake mix, breadcrumbs, etc.), seasonings (sauces, tomato-processed seasonings, flavor seasonings, cooking mixes, soups, etc.), and processed livestock products (livestock ham, sausages, etc.).

[0025] The above foods may contain various nutrients, various vitamins (vitamin A, vitamin B1, vitamin B2, vitamin B6, vitamin C, vitamin D, vitamin E, vitamin K, etc.), various minerals (magnesium, zinc, iron, sodium, potassium, selenium, etc.), dietary fiber, stabilizers such as dispersants and emulsifiers, sweeteners, flavoring ingredients (citric acid, malic acid, etc.), flavors, royal jelly, propolis, agaricus, etc., as needed.

[0026] When the composition of the present invention is used as a feed or a feed additive, examples of the feed include pet food, livestock or aquaculture feed additives, and the like.

[0027] Subjects to which the compositions of the present invention may be administered or ingested include humans and non-human animals (e.g., dogs, cats, mice, rats, hamsters, guinea pigs, rabbits, pigs, cows, chickens, parakeets, mynah birds, goats, horses, sheep, monkeys, etc.).

[0028] The amount of administration or intake of the composition of the present invention varies depending on the subject, target disease, symptoms, administration or intake route, etc., but for example, the long-chain hydroxylated fatty acid contained in the composition of the present invention can be administered orally or parenterally at a daily dose of 0.1 to 100 mg / kg body weight, preferably 0.2 to 50 mg / kg body weight, and more preferably 0.5 to 30 mg / kg body weight. Administration or intake may be divided into multiple doses per day. The amount may also be increased or decreased depending on the symptoms.

[0029] The present invention will be described in more detail with reference to the following examples, but these examples are merely illustrative of the present invention and are not intended to limit the scope of the present invention in any way. [Example 1]

[0030] Effects of hydroxylated fatty acids on muscle atrophy (immobilized) mouse models. Male C57BL / 6J mice (10 weeks old) were fed a standard diet (CE-2, Clea Japan), a 1% linoleic acid-containing diet (LA), or a 1% 10-hydroxy-cis-12-octadecenoic acid-containing diet (HYA) (LA was from Sigma-Aldrich, and HYA was from Noster) for 10 days. Then, under general anesthesia, both hind limbs were immobilized in plastic casts to create immobilized mouse models. After 10 days of immobilization (still receiving the standard diet or each of the mixed diets), the mice were sacrificed and weighed. Both soleus muscles were then harvested and weighed. The amount of food consumed on the standard diet and each of the mixed diets is shown in Figure 1. Figure 2 shows the comparison of muscle weight per body weight (n = 6, *P < 0.05, **P < 0.01, 2-way ANOVA with Bonferroni's post hoc test). Furthermore, both gastrocnemius muscles were harvested and weighed under the same conditions. Figure 3 shows the comparison of gastrocnemius muscle weight per body weight (n = 6, *P < 0.05, **P < 0.01, 2-way ANOVA with Bonferroni's post hoc test). The soleus muscles were immersed in formalin, cut at their maximum diameter, and then stained with HE to measure the cross-sectional area of ​​the muscle fibers. Figure 4 shows the comparison of soleus muscle cross-sectional area (the area of ​​400 fibers pooled from 2 mice was measured and averaged for each condition, **P < 0.01, 2-way ANOVA with Bonferroni's post hoc test).

[0031] There was no significant difference in food intake between the mice in each treatment group. In immobilized model mice, HYA administration significantly inhibited the loss of soleus, gastrocnemius, and soleus muscle cross-sectional area compared to normal diet administration. Similarly, in immobilized model mice, HYA administration significantly inhibited the loss of gastrocnemius and soleus muscle cross-sectional area compared to linoleic acid administration. On the other hand, in immobilized model mice, linoleic acid administration did not significantly inhibit the loss of soleus, gastrocnemius, and soleus muscle cross-sectional area compared to normal diet administration.

[0032] Example 2: Effects of Hydroxylated Fatty Acids on Muscle Atrophy Model Mice (High-Fat Diet-Fed Mice) Male C57BL / 6J mice (10 weeks old) were fed a normal diet (CE-2, CLEA Japan), a high-fat diet (HFD32, CLEA Japan), a high-fat diet supplemented with 1% HYA, or a high-fat diet supplemented with 1% LA (linoleic acid) (HYA prepared by Noster Corporation, LA prepared by Sigma-Aldrich) for 14 days to generate a high-fat diet-induced muscle atrophy model mouse, and the effects of hydroxylated fatty acid administration were evaluated. (1) Effects of High-Fat Diet Intake on Body Weight, etc. Body weight measurements for each treatment group after 14 days of feeding are shown in Figure 5 (n = 12, *P < 0.05, 2-way ANOVA with Bonferroni's post hoc test). This study demonstrated that the high-fat diet group had a significantly greater weight gain than the normal diet group. In addition, an oral glucose tolerance test (OGTT) was performed on each treatment group after the 14-day feeding period. The AUC (area under the curve) of blood glucose levels is shown in Figure 6 (n = 5). This test showed that blood glucose levels tended to increase significantly in the high-fat diet group compared to the normal diet group, although the difference was not significant. These test results suggest that the high-fat diet-induced muscle atrophy mouse model is suitable for evaluating, for example, muscle atrophy due to obesity, muscle atrophy due to diabetes, and muscle atrophy due to metabolic disorders.

[0033] (2) Effects of Hydroxylated Fatty Acids. Male C57BL / 6J mice (10 weeks old) were fed a normal diet (CE-2, CLEA Japan), a high-fat diet (HFD32, CLEA Japan), a high-fat diet supplemented with 1% HYA, or a high-fat diet supplemented with 1% linoleic acid (LA) for 14 days. After each diet, the mice were sacrificed, weighed, and both soleus muscles were collected and weighed. Figure 7 shows the results of a comparison of soleus muscle weight per body weight (n = 12, **P < 0.01, 2-way ANOVA with Bonferroni's post hoc test). Furthermore, both gastrocnemius muscles were collected and weighed under the same conditions. Figure 8 shows the results of a comparison of gastrocnemius muscle weight per body weight (n = 12, **P < 0.01, 2-way ANOVA with Bonferroni's post hoc test). The formalin-soaked tibialis anterior muscles were cut at their maximum diameter cross-section to prepare sections, which were then stained with HE (Fig. 9(A)). The cross-sectional area of ​​the muscle fibers was then measured. The results of a comparison of the cross-sectional area of ​​the tibialis anterior muscles are shown in Fig. 9(B) (The area of ​​400 fibers pooled from 2 mice was measured and averaged for each condition, **P < 0.01, 2-way ANOVA with Bonferroni's post hoc test).

[0034] In mice fed a high-fat diet, soleus muscle weight, gastrocnemius muscle weight and tibialis anterior muscle cross-sectional area were all significantly decreased by high-fat diet compared with normal diet.On the other hand, by administering HYA in combination, soleus muscle weight, gastrocnemius muscle weight and tibialis anterior muscle cross-sectional area were all significantly increased compared with high-fat diet alone, showing a significant improvement effect.On the other hand, when linoleic acid was administered in combination, soleus muscle weight, gastrocnemius muscle weight and tibialis anterior muscle cross-sectional area all showed an increase tendency compared with high-fat diet alone, but it was not significant.

[0035] While the present invention has been described with emphasis on preferred embodiments, it will be apparent to those skilled in the art that the preferred embodiments may be modified.

[0036] The present invention has revealed that long-chain hydroxylated fatty acids have a previously unknown physiological function: the inhibitory effect of muscle atrophy. Compositions containing such long-chain hydroxylated fatty acids that inhibit muscle atrophy can be applied in various fields, such as pharmaceuticals, foods, and feeds, making the present invention extremely useful industrially.

[0037] This application is based on patent application No. 2023-140522 filed in Japan (filing date: August 30, 2023), the contents of which are incorporated in their entirety herein.

Claims

1. A muscle atrophy inhibitor that contains long-chain hydroxylated fatty acids as an active ingredient.

2. The muscle atrophy inhibitor according to claim 1, wherein the long-chain hydroxylated fatty acid has 18 carbon atoms.

3. The muscle atrophy inhibitor according to claim 2, wherein the long-chain hydroxylated fatty acid has a hydroxyl group at the 10-position.

4. The muscle atrophy inhibitor according to claim 3, wherein the long-chain hydroxylated fatty acid having a hydroxyl group at the 10-position is 10-hydroxy-cis-12-octadecenoic acid.

5. A muscle atrophy inhibitor according to any one of claims 1 to 4 for preventing or treating a disease accompanied by muscle atrophy.

6. A muscle atrophy inhibitor according to any one of claims 1 to 4, which is used to improve muscle mass loss.

7. The muscle atrophy inhibitor according to claim 6, wherein the decrease in muscle mass is due to a decrease in activity caused by immobilization or the intake of a high-fat diet.

8. The muscle atrophy inhibitor according to claim 5, wherein the disease is sarcopenia, disuse muscle atrophy, muscle atrophy due to obesity, muscle atrophy due to diabetes, myopathy, cachexia, metabolic disorders, neurological (nervous disease), or cancer.

9. The muscle atrophy inhibitor according to claim 8, wherein the myopathy is muscular dystrophy, distal myopathy, congenital myopathy, glycogen storage disease, mitochondrial myopathy, steroid myopathy, alcoholic myopathy, rhabdomyolysis, or myasthenia gravis.

10. A muscle atrophy inhibitor according to any one of claims 1 to 4, which is a pharmaceutical.

11. A composition for improving loss of muscle mass, comprising a long-chain hydroxylated fatty acid.

12. The composition according to claim 11, wherein the long-chain hydroxylated fatty acid has 18 carbon atoms.

13. The composition according to claim 12, wherein the long-chain hydroxylated fatty acid has a hydroxyl group at the 10-position.

14. The composition according to claim 13, wherein the long-chain hydroxylated fatty acid having a hydroxyl group at the 10-position is 10-hydroxy-cis-12-octadecenoic acid.

15. The composition according to any one of claims 11 to 14, wherein the loss of muscle mass is due to a decrease in activity caused by immobilization or a loss of muscle mass associated with the intake of a high-fat diet.

16. The composition according to any one of claims 11 to 14, wherein the loss of muscle mass is due to metabolic abnormalities, neurological (nerve disease), or cancer.

17. The composition according to any one of claims 11 to 14, which is a pharmaceutical product.

18. The composition according to any one of claims 11 to 14, which is a food product or a food additive.

19. The composition according to any one of claims 11 to 14, which is a feed or feed additive.

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