{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T17:03:17Z","timestamp":1792602197483,"version":"4.5.0"},"reference-count":40,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T00:00:00Z","timestamp":1748995200000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2025,6]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n Skeletal muscle atrophy and insulin resistance (IR) aggravate each other. Vitamin K2 (VK2) exhibits beneficial effects on IR, but whether it improves IR associated skeletal muscle atrophy remains insufficiently understood. This study aims to investigate the effects of VK2 on IR associated skeletal muscle atrophy in high\u2010fat diet (HFD) mice and type 2 diabetes mellitus (T2DM) patients and explore the potential mechanisms.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n VK2 was administered to HFD\u2010fed C57BL\/6 mice for 16\u2009weeks. Grip strength, exercise capacity, oral glucose tolerance test (OGTT) and body fat rate were measured. Animals were sacrificed, and skeletal muscle and serum samples were collected to analyse muscle atrophy, glucose and lipid levels. The gene expression profile of skeletal muscle was determined by RNA sequencing. C2C12 cells were cultured for gene knockdown and overexpression experiments. For the randomized controlled trial (RCT), a total of 102 T2DM patients aged 50\u201380\u2009years were recruited and randomly assigned to receive yogurt (one cup per day) with or without VK2 fortification (90\u2009\u03bcg\/day) for 6\u2009months. Grip strength, skeletal muscle mass (SM), skeletal muscle mass index (SMI), 6\u2010m gait speed (6\u2010m GS), glycated haemoglobin (HbA1c), fasting blood glucose (FBG), fasting insulin (FINS) and homeostasis model assessment of insulin resistance (HOMA\u2010IR) were measured at 0, 3 and 6\u2009months, respectively.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n VK2 significantly improved grip strength (\n p<\/jats:italic>\n \u2009<\u20090.01) and exercise capacity (all\n p<\/jats:italic>\n \u2009<\u20090.05) in HFD\u2010fed mice. At the tissue level, VK2 increased skeletal muscle mass (\n p<\/jats:italic>\n \u2009<\u20090.05) and cross\u2010sectional area of muscle fibres (\n p<\/jats:italic>\n \u2009<\u20090.05), while reducing the proportion of fast\u2010twitch fibres (\n p<\/jats:italic>\n \u2009<\u20090.01). VK2 treatment decreased body fat rate (\n p<\/jats:italic>\n \u2009<\u20090.01) accompanied by enhanced whole\u2010body energy metabolism. VK2 also diminished the glucolipid metabolism parameters, including glucose (\n p<\/jats:italic>\n \u2009<\u20090.01), HOMA\u2010IR (\n p<\/jats:italic>\n \u2009<\u20090.01) and serum lipid levels. Regarding the mechanism, VK2 promoted the phosphorylation of proteins in the FAK\u2010AKT\u2013mTOR\u2010P70S6K pathway by targeting Ccn2, thereby enhancing protein synthesis of C2C12 myotubes. In the RCT study, VK2 supplementation significantly increased grip strength (\n p<\/jats:italic>\n treatment\u2009\u00d7\u2009time<\/jats:sub>\n \u2009=\u20090.017), SM (\n p<\/jats:italic>\n treatment\u2009\u00d7\u2009time<\/jats:sub>\n \u2009=\u20090.001), SMI (\n p<\/jats:italic>\n treatment\u2009\u00d7\u2009time<\/jats:sub>\n < 0.001) and decreased HbA1c (\n p<\/jats:italic>\n treatment\u2009\u00d7\u2009time<\/jats:sub>\n < 0.001), FBG (\n p<\/jats:italic>\n treatment\u2009\u00d7\u2009time<\/jats:sub>\n \u2009=\u20090.056), FINS (\n p<\/jats:italic>\n treatment\u2009\u00d7\u2009time<\/jats:sub>\n < 0.001), and HOMA\u2010IR (\n p<\/jats:italic>\n treatment\u2009\u00d7\u2009time<\/jats:sub>\n < 0.001) in T2DM subjects.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Our findings demonstrated the beneficial effects of VK2 on insulin resistance related skeletal muscle atrophy by promoting protein synthesis via the AKT\/mTOR pathway.<\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/jcsm.13840","type":"journal-article","created":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T05:43:38Z","timestamp":1749015818000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Vitamin K2 Alleviates Insulin Resistance Associated Skeletal Muscle Atrophy via the AKT\/mTOR Signalling Pathway"],"prefix":"10.1002","volume":"16","author":[{"given":"Yingfeng","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Nutrition and Food Hygiene School of Public Health, Harbin Medical University Harbin China"},{"name":"Department of Clinical Nutrition Zigong First People's Hospital Zigong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yina","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Hygiene School of Public Health, Harbin Medical University Harbin 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7595-2474","authenticated-orcid":false,"given":"Ying","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Hygiene School of Public Health, Harbin Medical University Harbin China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,6,4]]},"reference":[{"key":"e_1_2_9_2_1","first-page":"12","article-title":"Potential Therapeutic Strategies for Skeletal Muscle Atrophy","volume":"12","author":"Huang L.","year":"2022","journal-title":"Antioxidants 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