{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T03:46:20Z","timestamp":1790221580412,"version":"4.1.0"},"reference-count":53,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2025,7,9]],"date-time":"2025-07-09T00:00:00Z","timestamp":1752019200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Rural Development Administration, Republic of Korea","award":["PJ016207"],"award-info":[{"award-number":["PJ016207"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>As life expectancy increases, muscle atrophy, characterized by a decline in muscle mass and strength that can impair mobility, has become a growing concern, highlighting the potential of protein supplementation as a promising intervention strategy. A horse meat hydrolysate, with a molecular weight of less than 3 kDa, derived from m. biceps femoris and produced using the food-grade enzyme Alcalase\u00ae (A4 &lt; 3kDa) was evaluated for its efficacy in mitigating dexamethasone-induced muscle atrophy, a widely accepted model for studying catabolic muscle loss. Administered orally to C57BL\/6 mice at dosages of 200 mg\/kg or 500 mg\/kg body weight for 35 days, A4 &lt; 3kDa effectively countered the weight loss induced by dexamethasone in the whole body, quadriceps, tibialis anterior, and gastrocnemius muscles. Moreover, it increased muscle fiber cross-sectional area and grip strength. These effects were attributed to increased protein synthesis via the protein kinase B (AKT)\/forkhead box O3 (FoxO3a)\/mammalian target of rapamycin (mTOR) signaling pathway. A4 &lt; 3kDa augmented the phosphorylation of key components of the signaling pathways associated with muscle atrophy, resulting in reduced mRNA expression of Atrogin-1 and MuRF-1. These findings demonstrate the potential of A4 &lt; 3kDa as a functional food ingredient for preventing muscle atrophy.<\/jats:p>","DOI":"10.3390\/cells14141050","type":"journal-article","created":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T07:38:27Z","timestamp":1752133107000},"page":"1050","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Horse Meat Hydrolysate Ameliorates Dexamethasone-Induced Muscle Atrophy in C57BL\/6 Mice via the AKT\/FoxO3a\/mTOR Pathway"],"prefix":"10.3390","volume":"14","author":[{"given":"Hee-Jeong","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Applied Animal Science, Kangwon National University, Chuncheon 24341, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongwook","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Applied Animal Science, Kangwon National University, Chuncheon 24341, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2095-2394","authenticated-orcid":false,"given":"Yousung","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Applied Animal Science, Kangwon National University, Chuncheon 24341, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soomin","family":"Oh","sequence":"additional","affiliation":[{"name":"Department of Applied Animal Science, Kangwon National University, Chuncheon 24341, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9388-2126","authenticated-orcid":false,"given":"Cho Hee","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Nursing, Kangwon National University, Chuncheon 24341, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aera","family":"Jang","sequence":"additional","affiliation":[{"name":"Department of Applied Animal Science, Kangwon National University, Chuncheon 24341, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1007\/s00223-014-9915-y","article-title":"Skeletal muscle: A brief review of structure and function","volume":"96","author":"Frontera","year":"2015","journal-title":"Calcif. Tissue Int."},{"key":"ref_2","unstructured":"(2025, April 02). United States Census Bureau, Available online: https:\/\/www.census.gov\/library\/stories\/2023\/11\/world-population-estimated-eight-billion.html."},{"key":"ref_3","first-page":"412","article-title":"Sarcopenia: European consensus on definition and diagnosis: Report of the European Working Group on Sarcopenia in Older People","volume":"4","author":"Baeyens","year":"2010","journal-title":"Age Ageing"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1093\/ageing\/afy169","article-title":"Sarcopenia: Revised European consensus on definition and diagnosis","volume":"48","author":"Bahat","year":"2019","journal-title":"Age Ageing"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"987","DOI":"10.2165\/00007256-200838120-00003","article-title":"Cross-sectional area and muscular strength","volume":"38","author":"Jones","year":"2008","journal-title":"Int. J. Sports Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1152\/jappl.1994.77.2.493","article-title":"Myosin isoforms in mammalian skeletal muscle","volume":"77","author":"Schiaffino","year":"1994","journal-title":"J. Appl. Physiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1093\/gerona\/50A.Special_Issue.11","article-title":"Human aging, muscle mass, and fiber type composition","volume":"50","author":"Evans","year":"1995","journal-title":"J. Gerontol. A Biol. Sci. Med. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2069","DOI":"10.1111\/j.1532-5415.2010.03150.x","article-title":"Characteristics of muscle fiber type are predictive of skeletal muscle mass and strength in elderly men","volume":"58","author":"Verdijk","year":"2010","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Ayroldi, E., Cannarile, L., Adorisio, S., Delfino, D.V., and Riccardi, C. (2018). Role of endogenous glucocorticoids in cancer in the elderly. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19123774"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"115490","DOI":"10.1016\/j.jep.2022.115490","article-title":"Psoralea corylifolia L. seed extract attenuates dexamethasone-induced muscle atrophy in mice by inhibition of oxidative stress and inflammation","volume":"296","author":"Seo","year":"2022","journal-title":"J. Ethnopharmacol."},{"key":"ref_11","first-page":"4","article-title":"Exploring oral function, protein intake, and risk of sarcopenia: A scoping review","volume":"1","author":"Moynihan","year":"2024","journal-title":"JDR Clin. Trans. Res."},{"key":"ref_12","unstructured":"Lee, J., Oh, J., Kang, J., and Yoon, Y. Effect of Goat Meat on Alleviating Muscle Atrophy Induced by Dexamethasone in Mice, Food Sci. Anim. Resour., in press."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1007\/s40520-016-0709-0","article-title":"Nutrition, frailty, and sarcopenia","volume":"29","author":"Kiesswetter","year":"2017","journal-title":"Aging Clin. Exp. Res."},{"key":"ref_14","unstructured":"Ahmad, R.S., Imran, A., and Hussain, M.B. (2018). Meat Science and Nutrition, Intechopen. [1st ed.]."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Deldicque, L. (2020). Protein intake and exercise-induced skeletal muscle hypertrophy: An update. Nutrients, 7.","DOI":"10.3390\/nu12072023"},{"key":"ref_16","first-page":"62","article-title":"Chemical composition of horse meat","volume":"11","author":"Njari","year":"2009","journal-title":"Meso"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1177\/0884533613507607","article-title":"The role of dietary protein intake in the prevention of sarcopenia of aging","volume":"28","author":"Beasley","year":"2013","journal-title":"Nutr. Clin. Pract."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"74","DOI":"10.5851\/kosfa.2019.e86","article-title":"Texture Characteristics of Horse Meat for the Elderly Based on the Enzyme Treatment","volume":"40","author":"Kim","year":"2020","journal-title":"Food Sci. Anim. Resour."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1111\/j.1365-2621.1999.tb12268.x","article-title":"Functional properties of fish protein hydrolysate from herring (clupea harengus)","volume":"64","author":"Gesualdo","year":"1999","journal-title":"J. Food Sci."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Islam, M., Huang, Y., Islam, S., Fan, B., Tong, L., and Wang, F. (2022). Influence of the degree of hydrolysis on functional properties and antioxidant activity of enzymatic soybean protein hydrolysates. Molecules, 18.","DOI":"10.3390\/molecules27186110"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"132","DOI":"10.5851\/kosfa.2023.e65","article-title":"Effects of Horse Meat Hydrolysate on Oxidative Stress, Proinflammatory Cytokines, and the Ubiquitin-Proteasomal System of C2C12 Cells","volume":"44","author":"Lee","year":"2024","journal-title":"Food Sci. Anim. Resour."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Jeon, H., Kim, Y.T., Jang, W.Y., Kim, J.Y., Heo, K., Shim, J.J., Lee, J.L., Yang, D.C., and Kang, S.C. (2022). Effects of Lactobacillus curvatus HY7602-fermented antlers in dexamethasone-induced muscle atrophy. Fermentation, 8.","DOI":"10.3390\/fermentation8090454"},{"key":"ref_23","first-page":"89","article-title":"Skeletal muscle fiber types in C57BL6J mice","volume":"21","author":"Augusto","year":"2017","journal-title":"J. Morphol. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1152\/physiolgenomics.00219.2007","article-title":"Short-term high fat-feeding results in morphological and metabolic adaptations in the skeletal muscle of C57BL\/6J mice","volume":"32","author":"Mohren","year":"2008","journal-title":"Physiol Genom."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Fappi, A., de Carvalho Neves, J., Sanches, L.N., e Silva, P.V.M., Sikusawa, G.Y., Brand\u00e3o, T.P.C., Chadi, G., and Zanoteli, E. (2019). Skeletal Muscle Response to Deflazacort, Dexamethasone and Methylprednisolone. Cell J., 8.","DOI":"10.3390\/cells8050406"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Jeon, S.H., and Choung, S.Y. (2021). Oyster hydrolysates attenuate muscle atrophy via regulating protein turnover and mitochondria biogenesis in C2C12 cell and immobilized mice. Nutrients, 13.","DOI":"10.3390\/nu13124385"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Wang, P., Kang, S.Y., Kim, S.J., Park, Y.K., and Jung, H.W. (2022). Monotropein improves dexamethasone-induced muscle atrophy via the AKT\/mTOR\/FOXO3a signaling pathways. Nutrients, 14.","DOI":"10.3390\/nu14091859"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Oh, J., Park, S.H., Kim, D.S., Choi, W., Jang, J., Rahmawati, L., Jang, W.Y., Lim, H.K., Hwang, J.Y., and Gu, G.R. (2023). The Preventive Effect of Specific Collagen Peptides against Dexamethasone-Induced Muscle Atrophy in Mice. Molecules, 28.","DOI":"10.3390\/molecules28041950"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.5352\/JLS.2013.23.9.1147","article-title":"Antioxidation effect of leg bone extracts and enzyme hydrolysates from Jeju crossbred horses (Jeju native horse\u00d7 Thoroughbred)","volume":"23","author":"Kim","year":"2013","journal-title":"J. Life Sci."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Lanza, M.B., Martins-Costa, H.C., De Souza, C.C., Lima, F.V., Diniz, R.C., and Chagas, M.H. (2022). Muscle volume vs. anatomical cross-sectional area: Different muscle assessment does not affect the muscle size-strength relationship. J. Biomech., 132.","DOI":"10.1016\/j.jbiomech.2022.110956"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3081","DOI":"10.1093\/hmg\/ddx192","article-title":"Sialic acid deficiency is associated with oxidative stress leading to muscle atrophy and weakness in GNE myopathy","volume":"26","author":"Cho","year":"2017","journal-title":"Hum. Mol. Genet."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1002\/mus.23632","article-title":"Decreased surface sialic acid content is a sensitive indicator of muscle damage","volume":"47","author":"Iwata","year":"2013","journal-title":"Muscle Nerve"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/S0014-5793(04)00164-4","article-title":"Novel biological function of sialic acid (N-acetylneuraminic acid) as a hydrogen peroxide scavenger","volume":"561","author":"Iijima","year":"2004","journal-title":"FEBS Lett."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Jahan, M., Thomson, P.C., Wynn, P.C., and Wang, B. (2023). Red Meat Derived Glycan, N-acetylneuraminic Acid (Neu5Ac) Is a Major Sialic Acid in Different Skeletal Muscles and Organs of Nine Animal Species\u2014A Guideline for Human Consumers. Foods, 12.","DOI":"10.3390\/foods12020337"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1093\/glycob\/11.8.685","article-title":"Molecular cloning of a unique CMP\u2013sialic acid synthetase that effectively utilizes both deaminoneuraminic acid (KDN) and N-acetylneuraminic acid (Neu5Ac) as substrates","volume":"11","author":"Nakata","year":"2001","journal-title":"Glycobiology"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Yoshikawa, M., Hosokawa, M., Miyashita, K., Nishino, H., and Hashimoto, T. (2021). Effects of fucoxanthin on the inhibition of dexamethasone-induced skeletal muscle loss in mice. Nutrients, 13.","DOI":"10.3390\/nu13041079"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1704","DOI":"10.1126\/science.1065874","article-title":"Identification of ubiquitin ligases required for skeletal muscle atrophy","volume":"294","author":"Bodine","year":"2001","journal-title":"Science"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1152\/japplphysiol.01383.2003","article-title":"Contraction-mediated mTOR, p70S6k, and ERK1\/2 phosphorylation in aged skeletal muscle","volume":"97","author":"Parkington","year":"2004","journal-title":"J. Appl. Physiol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Lee, M.K., Jeong, H.H., Kim, M.J., Ryu, H., Baek, J., and Lee, B. (2022). Nutrients against glucocorticoid-induced muscle atrophy. Foods, 11.","DOI":"10.3390\/foods11050687"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"249","DOI":"10.5713\/ajas.18.0159","article-title":"Comparative study of nutritional composition and color traits of meats obtained from the horses and Korean native black pigs raised in Jeju Island","volume":"32","author":"Seong","year":"2019","journal-title":"Asian Australas. J. Anim. Sci."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Shin, J.E., Park, S.J., Ahn, S.I., and Choung, S.Y. (2020). Soluble whey protein hydrolysate ameliorates muscle atrophy induced by immobilization via regulating the PI3K\/Akt pathway in C57BL\/6 mice. Nutrients, 12.","DOI":"10.3390\/nu12113362"},{"key":"ref_42","first-page":"183","article-title":"What do we really know about the ubiquitin-proteasome pathway in muscle atrophy?","volume":"4","author":"Jagoe","year":"2001","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1016\/j.mad.2006.07.005","article-title":"Atrophy-related ubiquitin ligases, atrogin-1 and MuRF1 are up-regulated in aged rat Tibialis Anterior muscle","volume":"127","author":"Clavel","year":"2006","journal-title":"Mech. Ageing Dev."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"105419","DOI":"10.1016\/j.jff.2023.105419","article-title":"Extract of Alnus japonica prevents dexamethasone-induced muscle atrophy in mice","volume":"101","author":"Lee","year":"2023","journal-title":"J. Funct. Foods"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Han, M.J., Park, S.J., Lee, S.J., and Choung, S.Y. (2022). The Panax ginseng Berry extract and soluble whey protein hydrolysate mixture ameliorates sarcopenia-related muscular deterioration in aged mice. Nutrients, 14.","DOI":"10.3390\/nu14040799"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"E591","DOI":"10.1152\/ajpendo.00073.2004","article-title":"IGF-I stimulates muscle growth by suppressing protein breakdown and expression of atrophy-related ubiquitin ligases, atrogin-1 and MuRF1","volume":"287","author":"Sacheck","year":"2004","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1038\/84839","article-title":"Localized Igf-1 transgene expression sustains hypertrophy and regeneration in senescent skeletal muscle","volume":"27","author":"Musaro","year":"2001","journal-title":"Nat. Genet."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"4007","DOI":"10.1172\/JCI42447","article-title":"Distinct growth hormone receptor signaling modes regulate skeletal muscle development and insulin sensitivity in mice","volume":"120","author":"Mavalli","year":"2010","journal-title":"J. Clin. Investig."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1007\/s12020-012-9751-7","article-title":"Atrogin-1, MuRF-1, and sarcopenia","volume":"43","author":"Gumucio","year":"2013","journal-title":"Endocr. J."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2243","DOI":"10.3945\/jn.117.257873","article-title":"Long-term intake of a high-protein diet affects body phenotype, metabolism, and plasma hormones in mice","volume":"12","author":"Vu","year":"2017","journal-title":"J. Nutr."},{"key":"ref_51","first-page":"1018","article-title":"Biological characteristics of protein hydrolysates derived from Yoensan ogae meat by various commercial proteases","volume":"36","author":"Ha","year":"2019","journal-title":"J. Korean Soc. Appl. Sci. Technol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/j.foodchem.2007.08.036","article-title":"Antimicrobial and human cancer cell cytotoxic effect of synthetic angiotensin-converting enzyme (ACE) inhibitory peptides","volume":"107","author":"Jang","year":"2008","journal-title":"Food Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"135544","DOI":"10.1016\/j.foodchem.2023.135544","article-title":"Peptide profiles and allergy-reactivity of extensive hydrolysates of milk protein","volume":"411","author":"Cui","year":"2023","journal-title":"Food Chem."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/14\/14\/1050\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:07:18Z","timestamp":1760033238000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/14\/14\/1050"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,9]]},"references-count":53,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["cells14141050"],"URL":"https:\/\/doi.org\/10.3390\/cells14141050","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,9]]}}}