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As a condition of obesity accompanied by muscle mass loss and physical dysfunction, sarcopenic obesity (SO) has become a novel public health problem. Human fibroblast growth factor 19 (FGF19) plays a therapeutic role in metabolic diseases. However, the protective effects of FGF19 on skeletal muscle in obesity and SO are still not completely understood. Our results showed that FGF19 administration improved muscle loss and grip strength in young and aged mice fed a high\u2010fat diet (HFD). Increases in muscle atrophy markers (FOXO\u20103, Atrogin\u20101, MuRF\u20101) were abrogated by FGF19 in palmitic acid (PA)\u2010treated C2C12 myotubes and in the skeletal muscle of HFD\u2010fed mice. FGF19 not only reduced HFD\u2010induced body weight gain, excessive lipid accumulation and hyperlipidaemia but also promoted energy expenditure (PGC\u20101\u03b1, UCP\u20101, PPAR\u2010\u03b3) in brown adipose tissue (BAT). FGF19 treatment restored PA\u2010 and HFD\u2010induced hyperglycaemia, impaired glucose tolerance and insulin resistance (IRS\u20101, GLUT\u20104) and mitigated the PA\u2010 and HFD\u2010induced decrease in FNDC\u20105\/irisin expression. However, these beneficial effects of FGF19 on skeletal muscle were abolished by inhibiting AMPK, SIRT\u20101 and PGC\u20101\u03b1 expression. Taken together, this study suggests that FGF19 protects skeletal muscle against obesity\u2010induced muscle atrophy, metabolic derangement and abnormal irisin secretion partially through the AMPK\/SIRT\u20101\/PGC\u2010\u03b1 signalling pathway, which might be a potential therapeutic target for obesity and SO.<\/jats:p>","DOI":"10.1111\/jcmm.16448","type":"journal-article","created":{"date-parts":[[2021,3,10]],"date-time":"2021-03-10T03:53:25Z","timestamp":1615348405000},"page":"3585-3600","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":113,"title":["FGF19 protects skeletal muscle against obesity\u2010induced muscle atrophy, metabolic derangement and abnormal irisin levels via the AMPK\/SIRT\u20101\/PGC\u2010\u03b1 pathway"],"prefix":"10.1111","volume":"25","author":[{"given":"Ai","family":"Guo","sequence":"first","affiliation":[{"name":"Department of Geriatrics The First Affiliated Hospital of Chongqing Medical University 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