{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T20:48:10Z","timestamp":1792442890005,"version":"4.5.0"},"reference-count":29,"publisher":"Portland Press Ltd.","issue":"5","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,3,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Cardiac hypertrophy is a common pathophysiological process in various cardiovascular diseases, which still has no effective therapies. Irisin is a novel myokine mainly secreted by skeletal muscle and is believed to be involved in the regulation of energy metabolism. In the present study, we found that irisin expression was elevated in hypertrophic murine hearts and serum. Moreover, angiotension II-induced cardiomyocyte hypertrophy was attenuated after irisin administration and aggravated after irisin knockdown in vitro. Next, we generated transverse aortic constriction (TAC)-induced cardiac hypertrophy murine model and found that cardiac hypertrophy and fibrosis were significantly attenuated with improved cardiac function assessed by echocardiography after irisin treatment. Mechanistically, we demonstrated that FNDC5 was cleaved into irisin, at least partially, in a disintegrin and metalloproteinase (ADAM) family-dependent manner. ADAM10 was the candidate enzyme responsible for the cleavage. Further, we found irisin treatment activated AMPK and subsequently inhibited activation of mTOR. AMPK inhibition ablated the protective role of irisin administration. In conclusion, we find irisin is secreted in an ADAM family-dependent manner, and irisin treatment improves cardiac function and attenuates pressure overload-induced cardiac hypertrophy and fibrosis mainly through regulating AMPK-mTOR signaling.<\/jats:p>","DOI":"10.1042\/cs20190016","type":"journal-article","created":{"date-parts":[[2019,2,19]],"date-time":"2019-02-19T16:47:38Z","timestamp":1550594858000},"page":"611-627","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":109,"title":["FNDC5\/Irisin inhibits pathological cardiac hypertrophy"],"prefix":"10.1042","volume":"133","author":[{"given":"Qing","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Cardiology, Shanghai Tenth People\u2019s Hospital, School of Medicine, Tongji University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenxin","family":"Kou","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Shanghai Tenth People\u2019s Hospital, School of Medicine, Tongji University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Shanghai Tenth People\u2019s Hospital, School of Medicine, Tongji University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunping","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Shanghai Tenth People\u2019s Hospital, School of Medicine, Tongji University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peipei","family":"Luan","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Shanghai Tenth People\u2019s Hospital, School of Medicine, Tongji University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaopeng","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Shanghai Tenth People\u2019s Hospital, School of Medicine, Tongji University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hailing","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Shanghai Tenth People\u2019s Hospital, School of Medicine, Tongji University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhui","family":"Zhuang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Shanghai Tenth People\u2019s Hospital, School of Medicine, Tongji University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Shanghai Tenth People\u2019s Hospital, School of Medicine, Tongji University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yawei","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Shanghai Tenth People\u2019s Hospital, School of Medicine, Tongji University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2937-0024","authenticated-orcid":false,"given":"Wenhui","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Shanghai Tenth People\u2019s Hospital, School of Medicine, Tongji University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2019,3,1]]},"reference":[{"key":"2021113012301125500_B1","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1161\/CIRCULATIONAHA.108.845792","article-title":"The progression of hypertensive heart disease","volume":"123","author":"Drazner","year":"2011","journal-title":"Circulation"},{"key":"2021113012301125500_B2","doi-asserted-by":"publisher","first-page":"e67","DOI":"10.1161\/CIR.0000000000000558","article-title":"Heart Disease and Stroke Statistics-2018 Update: a report from the American Heart Association","volume":"137","author":"Benjamin","year":"2018","journal-title":"Circulation"},{"key":"2021113012301125500_B3","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1007\/s10741-016-9593-0","article-title":"Skeletal muscle inflammation and atrophy in heart failure","volume":"22","author":"Lavine","year":"2017","journal-title":"Heart Fail. 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