{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T00:11:26Z","timestamp":1793146286873,"version":"4.5.0"},"reference-count":91,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T00:00:00Z","timestamp":1769212800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Hubei Provincial Natural Science Foundation of China","award":["2024AFB963"],"award-info":[{"award-number":["2024AFB963"]}]},{"DOI":"10.13039\/501100019537","name":"Science Fund for Distinguished Young Scholars of Hubei Province","doi-asserted-by":"publisher","award":["2023AFA109"],"award-info":[{"award-number":["2023AFA109"]}],"id":[{"id":"10.13039\/501100019537","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Sarcopenic obesity, characterized by skeletal muscle loss concurrent with adipose tissue accumulation, has emerged as a global health threat. Exercise is established as an effective intervention; however, the molecular mechanisms underlying its protective effects remain incompletely defined. This study investigated whether exercise mitigates high-fat diet (HFD)-induced sarcopenic obesity, and whether the mechanism was related to the activation of the adenosine monophosphate-activated protein kinase (AMPK)\/Acetyl-CoA carboxylase pathway (ACC) pathway and the inhibition of ferroptosis. Cell experiments demonstrated that palmitic acid induced ferroptosis in C2C12 mouse myoblasts. Animal experiments confirmed that HFD promoted skeletal muscle ferroptosis in C57BL\/6 mice, evidenced by iron metabolism imbalance (solute carrier family 39 member14 upregulation, ferroportin downregulation), impaired antioxidant capacity (reduced glutathione, superoxide dismutase, glutathione peroxidase 4), and elevated lipid peroxidation (increased malondialdehyde). Meanwhile, both flat treadmill running and uphill treadmill running may reverse these changes by activating AMPK\/ACC phosphorylation, reducing non-transferrin iron uptake, enhancing iron export and storage, and improving antioxidant status, jointly inhibiting ferroptosis and attenuating muscle mass loss and lipid deposition. These findings confirm that ferroptosis acts as one of the key pathogenic drivers in sarcopenic obesity and suggests that exercise may improve sarcopenic obesity by activating the AMPK\/ACC pathway and inhibiting ferroptosis. This study provides novel mechanistic insights into exercise-mediated regulation of iron-lipid metabolism crosstalk and informs targeted interventions for sarcopenic obesity.<\/jats:p>","DOI":"10.3390\/ijms27031187","type":"journal-article","created":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T08:14:23Z","timestamp":1769415263000},"page":"1187","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Exercise Improves Sarcopenic Obesity Through Inhibition of Ferroptosis and Activation of the AMPK\/ACC Pathway"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2169-7471","authenticated-orcid":false,"given":"Qin","family":"Ru","sequence":"first","affiliation":[{"name":"Institute of Intelligent Sport and Proactive Health, Department of Health and Physical Education, Jianghan University, Wuhan 430056, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3313-1712","authenticated-orcid":false,"given":"Congyue","family":"Xu","sequence":"additional","affiliation":[{"name":"Institute of Intelligent Sport and Proactive Health, Department of Health and Physical Education, Jianghan University, Wuhan 430056, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chongzhou","family":"Wan","sequence":"additional","affiliation":[{"name":"Institute of Intelligent Sport and Proactive Health, Department of Health and Physical Education, Jianghan University, Wuhan 430056, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bei","family":"Cheng","sequence":"additional","affiliation":[{"name":"Institute of Intelligent Sport and Proactive Health, Department of Health and Physical Education, Jianghan University, Wuhan 430056, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Xiang","sequence":"additional","affiliation":[{"name":"Institute of Intelligent Sport and Proactive Health, Department of Health and Physical Education, Jianghan University, Wuhan 430056, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Fang","sequence":"additional","affiliation":[{"name":"Institute of Intelligent Sport and Proactive Health, Department of Health and Physical Education, Jianghan University, Wuhan 430056, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junqing","family":"Ren","sequence":"additional","affiliation":[{"name":"Institute of Intelligent Sport and Proactive Health, Department of Health and Physical Education, Jianghan University, Wuhan 430056, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Intelligent Sport and Proactive Health, Department of Health and Physical Education, Jianghan University, Wuhan 430056, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9041-4471","authenticated-orcid":false,"given":"Yuxiang","family":"Wu","sequence":"additional","affiliation":[{"name":"Institute of Intelligent Sport and Proactive Health, Department of Health and Physical Education, Jianghan University, Wuhan 430056, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"972","DOI":"10.1016\/S0140-6736(24)01210-8","article-title":"Obesity in adults","volume":"404","author":"Lingvay","year":"2024","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1038\/s41366-024-01530-6","article-title":"Obesity: A 100 year perspective","volume":"49","author":"Bray","year":"2025","journal-title":"Int. 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