Muscle atrophy inhibitor

Abstract

In one embodiment of the present application, disclosed is a muscle atrophy inhibitor containing a long-chain hydroxylated fatty acid as an active ingredient.

Description

TECHNICAL FIELD

[0001] The present application relates to a long-chain hydroxylated fatty acid that suppresses muscle atrophy, which is useful in the fields of medicine, food, and the like. BACKGROUND

[0002] In humans and animals, muscle mass gradually decreases with age or changes in lifestyle after middle age. With aging, muscle loss as muscle atrophy due to age becomes a problem. Muscle atrophy includes not only muscle loss, but also disuse atrophy in which muscle atrophies due to inactivity such as plaster fixation, bed rest, and the like, and myopathy such as neurogenic muscle disease, in which autonomous activity is inhibited. After autonomous activity is limited due to muscle atrophy, it has an impact on daily life and becomes a major social problem.

[0003] As a substance known to help maintain muscle function, 3-hydroxyisovaleric acid is known, and as a composition that improves its unique flavor improvement and muscle atrophy improvement effects, a composition containing 3-hydroxyisovaleric acid and an amino sugar is reported (Patent Literature 1). In addition, there is a report on the treatment and prevention of diseases associated with muscle atrophy by kynurenine, which is a metabolite of tryptophan (Patent Literature 2), and a report on a muscle atrophy inhibiting composition containing a tripeptide as an effective ingredient (Patent Literature 3). There is also a report of a gene expression control agent with an odd-numbered fatty acid as an effective ingredient, which suppresses muscle atrophy by inhibiting the expression of metallothionein-2 gene or promoting the expression of nucleoporin-210 gene (Patent Literature 4). It is also reported that muscle atrophy is inhibited by neutralizing antibodies to inhibit the expression of chemokine CXCL10 (Patent Literature 5).

[0004] In Non-Patent Literature 1, nutrients related to muscle synthesis were investigated, and it was reported that omega-3 fatty acids contribute to the promotion of muscle synthesis, while omega-6 fatty acids promote muscle protein breakdown and inhibit muscle hypertrophy.

[0005] There is a statistical analysis of a study that summarized muscle loss disease and omega-3 fatty acid and omega-6 fatty acid intake data (Non-Patent Literature 2), and the results reported a negative correlation between omega-3 fatty acid intake and the prevalence of muscle loss, suggesting a relationship between omega-3 fatty acid intake and muscle loss. In addition, Non-Patent Literature 3 considers muscle loss as an inflammatory disease, and suggests that the anti-inflammatory effect of omega-3 fatty acids can make them a therapeutic drug for muscle loss, but there are many unknowns about their effects.

[0006] As described above, although there are reports that 3-hydroxyisovaleric acid, amino acid metabolites, and peptides have an effect of inhibiting muscle atrophy, and there are reports suggesting the effect of omega-3 fatty acids on muscle loss, there have been no reports so far on the inhibition of muscle atrophy by long-chain hydroxylated fatty acids.

[0007] Prior art documents

[0008] Patent documents

[0009] Patent Document 1: Japanese Patent Application Publication No. 2016-88844

[0010] Patent Document 2: Japanese Patent Application Laid-Open No. 2019-530743

[0011] Patent Document 3: WO 2018 / 105550

[0012] Patent Document 4: Japanese Patent Application Laid-Open No. 2019-172614

[0013] Patent Document 5: Japanese Patent Application Laid-Open No. 2022-162858

[0014] Non-patent documents

[0015] Non-patent Document 1: Darren G. et al., Biogerontology (2012) 13:345-358

[0016] Non-patent Document 2: Yi Zhang et al., Frontiers in Nutrition, January 2022, Volume 8, Article 738083

[0017] Non-patent Document 3: Ahmed Al Saedi et al., Bone 164 (2022) 116539 SUMMARY

[0018] PROBLEMS TO BE SOLVED BY THE INVENTION

[0019] An object of the present application is to provide a functional fatty acid for inhibiting muscle atrophy, and to provide, in the form of embodiments, a drug and an improvement method for improving the health condition by inhibiting muscle atrophy caused by, for example, plaster fixation, aging, intake of high-fat food, metabolic abnormalities, neurological diseases, cancer, and the like.

[0020]

[0021] The present inventors have conducted intensive studies in view of the above problems, and as a result, have found that administration of a long-chain hydroxylated fatty acid to a mouse in which disuse of the hind limbs is used as a model of muscle atrophy can inhibit muscle atrophy. Further, it has been found that administration of a long-chain hydroxylated fatty acid can also inhibit muscle atrophy induced in a mouse by administration of a high-fat diet. Furthermore, among long-chain hydroxylated fatty acids, it has been found that a hydroxylated fatty acid having 18 carbon atoms and a hydroxyl group at the 10-position has a high muscle atrophy inhibitory effect, and thus the present application has been completed.

[0022] That is, the present application, as a specific embodiment thereof, provides the following. However, the present application is not limited to these.

[0023] [1] A muscle atrophy inhibitor containing a long-chain hydroxylated fatty acid as an effective ingredient.

[0024] [2] The muscle atrophy inhibitor according to [1], wherein the long-chain hydroxylated fatty acid has 18 carbon atoms.

[0025] [3] The muscle atrophy inhibitor according to [2], wherein the long-chain hydroxylated fatty acid has a hydroxyl group at the 10-position.

[0026] [4] The muscle atrophy inhibitor according to [3], wherein the long-chain hydroxylated fatty acid having a hydroxyl group at the 10-position is 10-hydroxy-cis-12-octadecenoic acid.

[0027] [5] The muscle atrophy inhibitor according to any one of [1] to [4], which is used for the prevention or treatment of a disease accompanied by muscle atrophy.

[0028] [6] The muscle atrophy inhibitor according to any one of [1] to [5], which is used for the improvement of a decrease in muscle mass.

[0029] [7] The muscle atrophy inhibitor according to [6], wherein the decrease in muscle mass is caused by a decrease in exercise amount due to disuse or intake of a high-fat diet.

[0030] [8] The muscle atrophy inhibitor according to [5], wherein the disease is Sarcopenia, disuse atrophy, atrophy caused by obesity, atrophy caused by diabetes, Myopathy, Cachexia, metabolic abnormality, neuropathy, i.e., a neurological disease, or cancer.

[0031] ​[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.

[0032]

[10] The muscle atrophy inhibitor according to any one of claims 1 to 9, which is a pharmaceutical product.

[0033]

[11] A composition for improving a decrease in muscle mass, which contains a long-chain hydroxylated fatty acid.

[0034]

[12] The composition according to

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

[0035]

[13] The composition according to

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

[0036]

[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.

[0037]

[15] The composition according to any one of

[11] to

[14] , wherein the decrease in muscle mass is a decrease in muscle mass caused by a decrease in exercise due to inactivity or intake of a high-fat food.

[0038]

[16] The composition according to any one of

[11] to

[14] , wherein the decrease in muscle mass is a decrease in muscle mass caused by a metabolic abnormality, a neurological disease, or cancer.

[0039]

[17] The composition according to any one of

[11] to

[14] , which is a pharmaceutical product.

[0040]

[18] The composition according to any one of

[11] to

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

[0041]

[19] The composition according to any one of

[11] to

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

[0042]

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

[0043]

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

[0044]

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

[0045] Effects of the Invention

[0046] The present application provides, as an embodiment thereof, an atrophy inhibitor, a composition for improving a decrease in muscle mass, and the like, which contain a long-chain hydroxylated fatty acid as an effective ingredient. The composition and the like are a composition and the like for inhibiting atrophy of muscle, which is caused by a decrease in exercise due to aging or immobilization such as plaster fixation, dietary habits such as intake of high-fat food, metabolic abnormalities, neuropathy (neurological diseases), cancer, and the like, and can be used in various fields such as pharmaceuticals, foods, and feed. BRIEF DESCRIPTION OF DRAWINGS

[0047] Figure 1 The intake amount when mice were made to ingest regular feed, linoleic acid mixed feed (LA), and 10-hydroxy-cis-12-octadecenoic acid mixed feed (HYA) is shown (Example 1 described later).

[0048] Figure 2 The soleus muscle weight after 20 days (including immobilization treatment for the latter 10 days) when mice were made to ingest regular feed, linoleic acid mixed feed (LA), and 10-hydroxy-cis-12-octadecenoic acid mixed feed (HYA) is shown (Example 1 described later).

[0049] Figure 3 The gastrocnemius muscle weight after 20 days (including immobilization treatment for the latter 10 days) when mice were made to ingest regular feed, linoleic acid mixed feed (LA), and 10-hydroxy-cis-12-octadecenoic acid mixed feed (HYA) is shown (Example 1 described later).

[0050] Figure 4 The cross-sectional area of muscle fibers when the soleus muscle was cut at the cross section along the maximum diameter after 20 days (including immobilization treatment for the latter 10 days) when mice were made to ingest regular feed, linoleic acid mixed feed (LA), and 10-hydroxy-cis-12-octadecenoic acid mixed feed (HYA) is shown (Example 1 described later).

[0051] Figure 5 The body weight measurement result after 14 days when mice were made to ingest regular feed, high-fat feed, high-fat feed added with 10-hydroxy-cis-12-octadecenoic acid (HYA), and high-fat feed added with linoleic acid (LA) is shown (Example 2 described later).

[0052] Figure 6 The measurement result of the blood glucose value AUC (area under the curve) after 14 days when mice were made to ingest regular feed, high-fat feed, high-fat feed added with 10-hydroxy-cis-12-octadecenoic acid (HYA), and high-fat feed added with linoleic acid (LA) is shown (Example 2 described later).

[0053] Figure 7 Muscle weight of soleus muscle after 14 days is shown when mice were made to ingest regular feed, high-fat feed, high-fat feed added with 10-hydroxy-cis-12-octadecenoic acid (HYA), high-fat feed added with linoleic acid (LA) (Example 2 described later).

[0054] Figure 8 Muscle weight of gastrocnemius muscle after 14 days is shown when mice were made to ingest regular feed, high-fat feed, high-fat feed added with 10-hydroxy-cis-12-octadecenoic acid (HYA), high-fat feed added with linoleic acid (LA) (Example 2 described later).

[0055] Figure 9 Results of HE staining of a section prepared by cutting a tibialis anterior muscle along a cross section at the maximum diameter after 14 days when mice were made to ingest regular feed, high-fat feed, high-fat feed added with 10-hydroxy-cis-12-octadecenoic acid (HYA), high-fat feed added with linoleic acid (LA) (Figure (A)), and comparison results of tibialis anterior muscle cross-sectional area (Figure (B)) are shown (Example 2 described later). DETAILED DESCRIPTION

[0056] The present application is explained in detail below, but unless otherwise specifically mentioned in the text, all technical and scientific terms used in this specification have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs. Any method and material equally or equivalently to those described in this specification can be used in the practice or testing of the present application, and preferred methods and materials are described below.

[0057] All publications, including patents and patent applications, cited in this specification are incorporated herein by reference in their entirety.

[0058] The present application provides an atrophy inhibitor, a composition for improving a decrease in muscle mass, and the like, containing a long-chain hydroxylated fatty acid. The long-chain hydroxylated fatty acid can include a fatty acid having 16 to 22 carbon atoms, and preferably a fatty acid having 18 carbon atoms. The hydroxylated fatty acid is preferably a hydroxylated fatty acid having a hydroxyl group at the 10 position.

[0059] More specifically, examples of long-chain hydroxylated fatty acids of the present invention include, but are not limited to: 10-hydroxy-cis-12-octadecanoic 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 known as HYB), 10-hydroxy-cis-15-octadecenoic acid (hereinafter also known as αHYB), 10-hydroxy-cis-6-octadecenoic acid (hereinafter also known as γHYB), 10-hydroxy-trans-11-octadecenoic acid (hereinafter also known as HYC), 10-hydroxy-trans-11,cis-15-octadecadienoic acid (hereinafter also known as αHYC), 10-hydroxy-cis-6,trans-11-octadecadienoic acid (hereinafter also known as γHYC), 10 -Hydroxy-cis-6,trans-11,cis-15-octadecanoic acid (hereinafter also known as sHYC), 10,13-dihydroxy-octadecanoic acid (hereinafter also known as HYE), 10,13-dihydroxy-cis-15-octadecanoic acid (hereinafter also known as αHYE), 10,13-dihydroxy-cis-6-octadecanoic acid (hereinafter also known as γHYE), 13-hydroxy-cis-9-octadecanoic acid (hereinafter also known as HYD), 13-hydroxy-cis-9 Cis-15-octadecadienoic acid (hereinafter also referred to as αHYD), 13-hydroxy-cis-6, cis-9-octadecadienoic acid (hereinafter also referred to as γHYD), 13-hydroxy-cis-6, cis-9, cis-15-octadecadienoic acid (hereinafter also referred to as sHYD), 13-hydroxy-cis-5, cis-9-octadecadienoic acid, and 13-hydroxy-trans-5, cis-9-octadecadienoic acid, etc., preferably 10-hydroxy-cis-12-octadecadienoic acid.

[0060] The long-chain hydroxylated fatty acids of the present invention can be prepared by known methods, for example, methods described in WO2013 / 168310 and WO2015 / 111699. Additionally, 10-hydroxy-cis-12-octadecenoic acid can be prepared with reference to Biochemical and Biophysical Research Communications 416(2011) pp.188-193, etc.

[0061] The muscle atrophy inhibitor and muscle mass reduction improvement composition containing long-chain hydroxylated fatty acids, as embodiments of the present invention, can be used to prevent or treat muscle atrophy, wherein the causes of muscle atrophy are not limited. Causes of muscle atrophy include plaster cast immobilization due to fractures, hospitalization or decreased physical activity due to aging, dietary habits such as high-fat diets, obesity, metabolic abnormalities, neurological diseases, and cancer. Diseases causing muscle atrophy due to these causes include disuse atrophy, sarcopenia, obesity-related muscle atrophy, diabetic muscle atrophy, myopathy, and cachexia.

[0062] Long-chain hydroxylated fatty acids, as one embodiment, can be used alone or formulated into a composition as described below (hereinafter collectively referred to as "the compositions of the present invention"). The compositions of the present invention can be used, for example, as pharmaceuticals, food, feed, etc., or mixed therein. When using the compositions of the present invention, they can also be used in combination with other pharmaceuticals, etc., as needed.

[0063] When the compositions of the present invention are used as pharmaceutical products, the dosage forms of such pharmaceutical products may include: powders, granules, pills, soft capsules, hard capsules, tablets, chewable tablets, disintegrating tablets, syrups, liquids, suspensions, etc. These preparations can be prepared according to conventional methods.

[0064] Additives that can be used in formulations include, for example: vegetable and animal oils such as soybean oil, safflower oil, olive oil, wheat germ oil, sunflower seed oil, tallow, and sardine oil; polyols such as polyethylene glycol, propylene glycol, glycerin, and sorbitol; surfactants such as sorbitan fatty acid esters, sucrose fatty acid esters, glycerol fatty acid esters, and polyglycerol fatty acid esters; excipients such as purified water, lactose, starch, crystalline cellulose, D-mannitol, lecithin, gum arabic, sorbitol solution, and sugar solution; sweeteners, colorants, pH adjusters, and flavorings. Liquid formulations can also be dissolved or suspended in water or other suitable media before administration. Furthermore, tablets and granules can be coated using known methods.

[0065] In cases where oral administration is difficult, it can be administered as enteral nutrition, or via nasogastric tube, gastrostomy, or enterostomy.

[0066] The compositions of the present invention can be used as food or food additives. As food, there are no particular limitations, for example, conventional foods, health foods, functional foods, nutritional supplements, health function foods (e.g., foods for specific health purposes, functionally labeled foods, and nutritionally functional foods) and foods for special purposes (e.g., infant foods, foods for pregnant and postpartum women, and foods for patients), etc.

[0067] Furthermore, the compositions of the present invention can also be provided and sold as food products labeled with uses related to inhibiting muscle atrophy, inhibiting muscle mass loss, and maintaining muscle mass.

[0068] Such “marking” behavior includes all actions taken to inform users of the above-mentioned uses. Any expression that can lead people to associate with or infer the above-mentioned uses, regardless of the purpose, content, object / media, etc., falls under the category of “marking” behavior in this embodiment.

[0069] There are no particular restrictions on labeling. For example, labels that claim to inhibit muscle atrophy, inhibit muscle mass reduction, and maintain muscle mass are preferred. Where necessary, labels for foods that have already been licensed or applied for (such as foods for specific health purposes, functional foods, and nutritional functional foods, as well as foods for special purposes) are preferred. Examples of such labels include "has the function of inhibiting muscle atrophy," "has the function of inhibiting muscle mass reduction," "has the function of inhibiting muscle strength reduction," "has the function of inhibiting muscle weakness," "has the function of assisting in maintaining muscle mass and strength," "has the function of improving walking ability," and "has the function of maintaining walking strength." Foods with licensed or applied-for functional labels can be distinguished from general foods.

[0070] When the composition of the present invention is used as a food or food additive, the food can be in the form of a solution, suspension, powder, solid molded product, or any other form that can be ingested orally, and there are no particular restrictions. Specific examples include: supplements (powders, granules, soft capsules, hard capsules, tablets, chewable tablets, disintegrating tablets, syrups, liquids, etc.); beverages (carbonated drinks, lactic acid bacteria drinks, sports drinks, fruit juice drinks, vegetable drinks, soy milk drinks, coffee drinks, tea drinks, powdered drinks, concentrated drinks, nutritional drinks, alcoholic drinks, etc.); snacks (gummy candies, jellies, chewing gum, chocolates, biscuits, candies, caramel, Japanese sweets, casual snacks, etc.); ready-to-eat foods (instant noodles, soft canned foods, canned foods, microwaveable foods, ready-to-eat soups / miso soups, freeze-dried foods, etc.); oils and oil-based foods (mayonnaise, salad dressing, butter, cream, margarine, etc.); wheat flour products (bread, pasta, noodles, cake mixes, breadcrumbs, etc.); seasonings (sauces, tomato-based seasonings, flavorings, cooking seasonings, broths, etc.); and processed animal products (ham, sausages, etc.).

[0071] The above-mentioned foods may be supplemented with various nutrients, vitamins (vitamin A, vitamin B1, vitamin B2, vitamin B6, vitamin C, vitamin D, vitamin E, vitamin K, etc.), minerals (magnesium, zinc, iron, sodium, potassium, selenium, etc.), dietary fiber, dispersants, emulsifiers and other stabilizers, sweeteners, flavoring ingredients (citric acid, malic acid, etc.), flavorings, royal jelly, propolis, agaric, etc., as needed.

[0072] When the composition of the present invention is used as feed or feed additive, examples of such feed include: pet food, livestock or aquaculture feed additives, etc.

[0073] As objects to which the compositions of the present invention are administered or ingested, examples include humans or animals other than humans (e.g., dogs, cats, mice, rats, hamsters, guinea pigs, rabbits, pigs, cattle, chickens, parrots, mynahs, goats, horses, sheep, monkeys, etc.).

[0074] The dosage or intake of the compositions of the present invention will vary depending on the recipient, target disease, symptoms, route of administration, etc. For example, the daily dosage or intake of the long-chain hydroxylated fatty acids contained in the compositions of the present invention is typically 0.1–100 mg / kg body weight, preferably 0.2–50 mg / kg body weight, and more preferably 0.5–30 mg / kg body weight, administered or ingested orally or non-orally. Administration or intake can be divided into multiple doses throughout the day. Furthermore, the dosage can be increased or decreased according to symptoms.

[0075] The present invention is illustrated in more detail by way of the following embodiments, but the embodiments are merely illustrative of the present invention and do not constitute any limitation on the scope of the present invention.

[0076] [Example 1]

[0077] Effects of hydroxylated fatty acids on muscular atrophy model mice (inactive mice)

[0078] C57BL / 6J male mice (10 weeks old) were fed a standard diet (CE-2, CLEA, Japan), a 1% linoleic acid mixed diet (LA), or a 1% 10-hydroxy-cis-12-octadecenoic acid mixed diet (HYA) for 10 days. (LA was manufactured by Sigma-Aldrich, and HYA was a product manufactured by Noster Corporation). After 10 days of immobilization (while continuing to be fed the standard diet or the mixed diet), the mice were sacrificed, and their body weight was measured. Bilateral soleus muscles were collected for weight measurement. The intake of the standard diet or the mixed diet is as follows: Figure 1 As shown. Furthermore, the comparison results of muscle mass per unit body weight are shown in... Figure 2(n = 6, *P < 0.05, **P < 0.01, 2-way ANOVA with Bonferroni's post hoc test). Additionally, under the same conditions, bilateral gastrocnemius muscle weights were measured. The comparison of gastrocnemius muscle weight per unit body weight is shown in... Figure 3 (n = 6, *P < 0.05, **P < 0.01, 2-way ANOVA with Bonferroni's post hoc test).

[0079] In addition, formalin-soaked soleus muscle was sectioned at its maximum diameter cross-section to prepare sections, and after HE staining, the cross-sectional area of ​​the muscle fibers was measured. The comparison results of the cross-sectional areas of the soleus muscle are shown below. Figure 4 (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).

[0080] No significant differences in intake were observed among the treatment groups. In inactive mouse models, the reduction in cross-sectional area of ​​the soleus, gastrocnemius, and soleus muscles was significantly inhibited by HYA administration compared to a standard diet. Similarly, in inactive mouse models, the reduction in cross-sectional area of ​​the gastrocnemius and soleus muscles was significantly inhibited by HYA administration compared to linoleic acid administration. On the other hand, in inactive mouse models, linoleic acid administration did not significantly inhibit the reduction in cross-sectional area of ​​the soleus, gastrocnemius, and soleus muscles compared to a standard diet.

[0081] [Example 2]

[0082] Effects of hydroxylated fatty acids on muscular atrophy model mice (mice fed a high-fat diet)

[0083] C57BL / 6J mice (male, 10 weeks old) were fed a regular diet (CE-2, CLEA, Japan), a high-fat diet (HFD32, CLEA, Japan), a diet with 1% HYA supplemented with high-fat, or a diet with 1% LA (linoleic acid) supplemented with high-fat (HYA was a product prepared by Noster Corporation, and LA was a product manufactured by Sigma-Aldrich) for 14 days to establish a muscular atrophy model mouse model fed a high-fat diet, and the effects of hydroxylated fatty acids were evaluated.

[0084] (1) Effects of high-fat diet intake on body weight, etc.

[0085] The body weight measurements of each treatment group after the above 14-day feeding period are shown in the figure. Figure 5 (n = 12, *P < 0.05, 2-way ANOVA with Bonferroni's post hoc test). This study showed that the high-fat diet group had a significantly greater body weight compared to the conventional diet group.

[0086] In addition, an oral glucose tolerance test (OGTT) was performed in each treatment group after 14 days of administration. Blood glucose AUC (area under the curve) is shown in [the figure]. Figure 6 (n = 5). This experiment showed that, compared with the conventional feed intake group, the blood glucose level in the high-fat feed intake group did not show a significant difference, but there was a tendency for a substantial increase.

[0087] The above experimental results indicate that the high-fat diet-administered muscular atrophy model mice are suitable for evaluating conditions such as "muscular atrophy caused by obesity", "muscular atrophy caused by diabetes", and "muscular atrophy caused by metabolic abnormalities".

[0088] (2) Effects of hydroxylated fatty acids

[0089] C57BL / 6J mice (male, 10 weeks old) were fed a standard diet (CE-2, CLEA, Japan), a high-fat diet (HFD32, CLEA, Japan), a diet supplemented with 1% HYA and high-fat, and a diet supplemented with 1% LA (linoleic acid) and high-fat for 14 days, respectively. Mice were then sacrificed, and body weight was measured. Bilateral soleus muscle was collected and its weight was measured. The comparison results of soleus muscle weight per unit body weight are shown in [Figure / Table / Insert Table ...Insert Table / In Figure 7 (n = 12, **P < 0.01, 2-way ANOVA with Bonferroni's post hoc test). Additionally, under the same conditions, bilateral gastrocnemius muscle weights were measured. Comparisons of gastrocnemius muscle weight per unit body weight are shown in...Figure 8 (n = 12, **P < 0.01, 2-way ANOVA with Bonferroni's post hoc test).

[0090] Meanwhile, the formalin-soaked tibialis anterior muscle was cut at its largest diameter cross-section to prepare sections for HE staining. Figure 9 (A) Afterwards, the cross-sectional area of ​​the muscle fibers was measured. The comparison results of the cross-sectional areas of the tibialis anterior muscle are shown in... Figure 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).

[0091] In mice fed a high-fat diet, compared with mice fed a regular diet, the weight of the soleus muscle, the weight of the gastrocnemius muscle, and the cross-sectional area of ​​the tibialis anterior muscle were all significantly reduced due to the high-fat diet.

[0092] In contrast, by combining HYA with other feeds, the weight of the soleus muscle, the weight of the gastrocnemius muscle, and the cross-sectional area of ​​the tibialis anterior muscle all increased significantly compared with the case of feeding high-fat feed alone, showing a clear improvement effect.

[0093] On the other hand, when linoleic acid was fed in combination, the weight of the soleus muscle, the weight of the gastrocnemius muscle, and the cross-sectional area of ​​the tibialis anterior muscle all showed an increasing tendency compared with the case of feeding high-fat diet alone, but the increase was not significant.

[0094] Although the present invention has been described above by emphasizing preferred embodiments, it will be apparent to those skilled in the art that the preferred embodiments may be modified.

[0095] [Industry Applicability]

[0096] This invention clarifies the physiological function of long-chain hydroxylated fatty acids, exhibiting a previously unknown effect in inhibiting muscle atrophy. Muscle atrophy-inhibiting compositions containing this long-chain hydroxylated fatty acid are applicable to various fields such as pharmaceuticals, food, and animal feed, making this invention extremely useful industrially.

[0097] This application is based on Japanese Special Application 2023-140522 filed in Japan (filed on August 30, 2023), the contents of which are fully contained in this specification.

Claims

1. A muscle atrophy inhibitor, characterized in that, It contains long-chain hydroxylated fatty acids as its active ingredient.

2. The muscle atrophy inhibitor according to claim 1, wherein, Long-chain hydroxylated fatty acids have 18 carbon atoms.

3. The muscle atrophy inhibitor according to claim 2, wherein, Long-chain hydroxylated fatty acids have a hydroxyl group at the 10 position.

4. The muscle atrophy inhibitor according to claim 3, wherein, Long-chain hydroxylated fatty acids with a hydroxyl group at position 10 are 10-hydroxy-cis-12-octadecenoic acid.

5. The muscular atrophy inhibitor according to any one of claims 1 to 4, used for the prevention or treatment of diseases accompanied by muscular atrophy.

6. The muscle atrophy inhibitor according to any one of claims 1 to 4, used to improve muscle mass reduction.

7. The muscle atrophy inhibitor according to claim 6, wherein, Muscle loss is caused by reduced physical activity due to inactivity or by the intake of high-fat foods.

8. The muscle atrophy inhibitor according to claim 5, wherein, The diseases include sarcopenia, disuse atrophy, obesity-related atrophy, diabetes-related atrophy, myopathy, cachexia, metabolic abnormalities, neurological diseases, or cancer.

9. The muscle atrophy inhibitor according to claim 8, wherein, Myopathy includes 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 claims 1 to 4, wherein it is a pharmaceutical product.

11. A composition for improving muscle mass reduction, characterized in that, It contains long-chain hydroxylated fatty acids.

12. The composition according to claim 11, wherein, Long-chain hydroxylated fatty acids have 18 carbon atoms.

13. The composition according to claim 12, wherein, Long-chain hydroxylated fatty acids have a hydroxyl group at the 10 position.

14. The composition according to claim 13, wherein, Long-chain hydroxylated fatty acids with a hydroxyl group at position 10 are 10-hydroxy-cis-12-octadecenoic acid.

15. The composition according to any one of claims 11 to 14, wherein, Muscle loss is caused by reduced physical activity due to inactivity or by the intake of high-fat foods.

16. The composition according to any one of claims 11 to 14, wherein, Muscle loss can be caused by metabolic abnormalities, neurological diseases, or cancer.

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

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

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

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