{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T05:02:21Z","timestamp":1784869341394,"version":"3.55.0"},"reference-count":131,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T00:00:00Z","timestamp":1784851200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005046","name":"Natural Science Foundation of Heilongjiang Province","doi-asserted-by":"publisher","award":["LH2022C051"],"award-info":[{"award-number":["LH2022C051"]}],"id":[{"id":"10.13039\/501100005046","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:p>Metabolic dysfunction-associated steatotic liver disease (MASLD) has become one of the most prevalent chronic liver diseases worldwide. Its disease spectrum can progress from simple hepatic steatosis to metabolic dysfunction-associated steatohepatitis (MASH), liver fibrosis, cirrhosis, and even hepatocellular carcinoma. Despite recent advancements in targeted pharmacological therapies for MASH, limitations persist regarding applicable populations and long-term benefits. Therefore, various lifestyle interventions, including dietary management and regular exercise, remain the cornerstone of MASLD management. AMP-activated protein kinase (AMPK), as an energy sensor, coordinates lipid synthesis, fatty acid oxidation, mitochondrial homeostasis, autophagy, and inflammatory responses under conditions of energy stress, thereby representing a key molecular hub connecting exercise, cold exposure, and the ameliorative effects on MASLD. Based on a narrative synthesis of mechanistic and translational evidence, this article summarizes the effects of exercise intervention, cold exposure, and their combination on AMPK-related pathways and further elucidates the potential mechanisms in terms of hepatic lipid metabolism, brown\/beige adipose thermogenesis, skeletal muscle-adipose tissue-liver interorgan crosstalk, and mitochondrial quality control. Current evidence, particularly from animal and mechanistic studies, suggests that exercise and cold exposure may regulate MASLD-related metabolic abnormalities through the AMPK\/ACC\/SREBP1c, AMPK\/SIRT1\/PGC-1\u03b1 and AMPK\/mTOR\/TFEB pathways, as well as AMPK-related myokine\/hepatokine networks. The combined intervention remains an emerging strategy; preclinical data indicate potential additive effects on energy expenditure and lipid clearance, but synergistic mechanisms, optimal temperature conditions, clinical safety, and long-term efficacy require further validation.<\/jats:p>","DOI":"10.3389\/fphys.2026.1865475","type":"journal-article","created":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T04:24:33Z","timestamp":1784867073000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Exercise and cold exposure as dual physiological stressors in MASLD: AMPK-mediated metabolic adaptation and interorgan crosstalk"],"prefix":"10.3389","volume":"17","author":[{"given":"Shijie","family":"Wang","sequence":"first","affiliation":[{"name":"Graduate School, Harbin Sport University","place":["Harbin, Heilongjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Gao","sequence":"additional","affiliation":[{"name":"Graduate School, Harbin Sport University","place":["Harbin, Heilongjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Wang","sequence":"additional","affiliation":[{"name":"Graduate School, Harbin Sport University","place":["Harbin, Heilongjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingfeng","family":"Wang","sequence":"additional","affiliation":[{"name":"Graduate School, Harbin Sport University","place":["Harbin, Heilongjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yufei","family":"Liu","sequence":"additional","affiliation":[{"name":"Laboratory Management Center, Harbin Sport University","place":["Harbin, Heilongjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"232","DOI":"10.15252\/emmm.201505610","article-title":"mTORC2 sustains thermogenesis via Akt-induced glucose uptake and glycolysis in brown adipose tissue","volume":"8","author":"Albert","year":"2016","journal-title":"EMBO Mol. 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