{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T21:09:41Z","timestamp":1790975381602,"version":"4.1.0"},"reference-count":63,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,7,13]],"date-time":"2021-07-13T00:00:00Z","timestamp":1626134400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>There is ongoing debate as to whether or not \u03b1-hydroxyisocaproic acid (HICA) positively regulates skeletal muscle protein synthesis resulting in the gain or maintenance of skeletal muscle. We investigated the effects of HICA on mouse C2C12 myotubes under normal conditions and during cachexia induced by co-exposure to TNF\u03b1 and IFN\u03b3. The phosphorylation of AMPK or ERK1\/2 was significantly altered 30 min after HICA treatment under normal conditions. The basal protein synthesis rates measured by a deuterium-labeling method were significantly lowered by the HICA treatment under normal and cachexic conditions. Conversely, myotube atrophy induced by TNF\u03b1\/IFN\u03b3 co-exposure was significantly improved by the HICA pretreatment, and this improvement was accompanied by the inhibition of iNOS expression and IL-6 production. Moreover, HICA also suppressed the TNF\u03b1\/IFN\u03b3 co-exposure-induced secretion of 3-methylhistidine. These results demonstrated that HICA decreases basal protein synthesis under normal or cachexic conditions; however, HICA might attenuate skeletal muscle atrophy via maintaining a low level of protein degradation under cachexic conditions.<\/jats:p>","DOI":"10.3390\/nu13072391","type":"journal-article","created":{"date-parts":[[2021,7,13]],"date-time":"2021-07-13T22:25:31Z","timestamp":1626215131000},"page":"2391","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["\u03b1-Hydroxyisocaproic Acid Decreases Protein Synthesis but Attenuates TNF\u03b1\/IFN\u03b3 Co-Exposure-Induced Protein Degradation and Myotube Atrophy via Suppression of iNOS and IL-6 in Murine C2C12 Myotube"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4191-1110","authenticated-orcid":false,"given":"Koichiro","family":"Sumi","sequence":"first","affiliation":[{"name":"Food Microbiology and Function Research Laboratories, R&D Division, Meiji Co. Ltd., 1-29-1 Nanakuni, Hachiouji, Tokyo 192-0919, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4757-0938","authenticated-orcid":false,"given":"Misato","family":"Sakuda","sequence":"additional","affiliation":[{"name":"Food Microbiology and Function Research Laboratories, R&D Division, Meiji Co. Ltd., 1-29-1 Nanakuni, Hachiouji, Tokyo 192-0919, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kinuyo","family":"Munakata","sequence":"additional","affiliation":[{"name":"Food Microbiology and Function Research Laboratories, R&D Division, Meiji Co. Ltd., 1-29-1 Nanakuni, Hachiouji, Tokyo 192-0919, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4083-0140","authenticated-orcid":false,"given":"Kentaro","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Food Microbiology and Function Research Laboratories, R&D Division, Meiji Co. Ltd., 1-29-1 Nanakuni, Hachiouji, Tokyo 192-0919, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4345-1170","authenticated-orcid":false,"given":"Kinya","family":"Ashida","sequence":"additional","affiliation":[{"name":"Food Microbiology and Function Research Laboratories, R&D Division, Meiji Co. Ltd., 1-29-1 Nanakuni, Hachiouji, Tokyo 192-0919, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1007\/s00253-003-1447-8","article-title":"Diversity of L-leucine catabolism in various microorganisms involved in dairy fermentations, and identification of the rate-controlling step in the formation of the potent flavour component 3-methylbutanal","volume":"64","author":"Smit","year":"2004","journal-title":"Appl. Microbiol. 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