{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T20:48:11Z","timestamp":1792442891985,"version":"4.5.0"},"reference-count":40,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2015,3,31]],"date-time":"2015-03-31T00:00:00Z","timestamp":1427760000000},"content-version":"vor","delay-in-days":30,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2015,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Chronic heart failure (CHF) is commonly associated with muscle atrophy and increased inflammation. Irisin, a myokine proteolytically processed by the fibronectin type III domain containing 5 (FNDC5) gene and suggested to be Peroxisome proliferator\u2010activated receptor gamma coactivator (PGC)\u20101\u03b1 activated, modulates the browning of adipocytes and is related to muscle mass. Therefore, we investigated whether skeletal muscle FNDC5 expression in CHF was reduced and if this was mediated by inflammatory cytokines and\/or angiotensin II (Ang\u2010II).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Skeletal muscle FNDC5 mRNA\/protein and PGC\u20101\u03b1 mRNA expression (arbitrary units) were analysed in: (i) rats with ischemic cardiomyopathy; (ii) mice injected with tumour necrosis factor\u2010\u03b1 (TNF\u2010\u03b1) (24\u2009h); (iii) mice infused with Ang\u2010II (4\u2009weeks); and (iv) C2C12 myotubes exposed to recombinant cytokines or Ang\u2010II. Circulating TNF\u2010\u03b1, Ang\u2010II, and irisin was measured by ELISA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Ischemic cardiomyopathy reduced significantly FNDC5 protein (1.3\u2009\u00b1\u20090.2 vs. 0.5\u2009\u00b1\u20090.1) and PGC\u20101\u03b1 mRNA expression (8.2\u2009\u00b1\u20091.5 vs. 4.7\u2009\u00b1\u20090.7).<jats:italic>In vivo<\/jats:italic>TNF\u2010\u03b1 and Ang\u2010II reduced FNDC5 protein expression by 28% and 45%, respectively. Incubation of myotubes with TNF\u2010\u03b1, interleukin\u20101\u00df, or TNF\u2010\u03b1\/interleukin\u20101\u00df reduced FNDC5 protein expression by 47%, 37%, or 57%, respectively, whereas Ang\u2010II had no effect. PGC\u20101\u03b1 was linearly correlated to FNDC5 in all conditions. In CHF, animals circulating TNF\u2010\u03b1 and Ang\u2010II were significantly increased, whereas irisin was significantly reduced. A negative correlation between circulating TNF\u2010\u03b1 and irisin was evident.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>A reduced expression of skeletal muscle FNDC5 in ischemic cardiomyopathy is likely modulated by inflammatory cytokines and\/or Ang\u2010II via the down\u2010regulation of PGC\u20101\u03b1. This may act as a protective mechanism either by slowing the browning of adipocytes and preserving energy homeostasis or by regulating muscle atrophy.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.12006","type":"journal-article","created":{"date-parts":[[2015,4,1]],"date-time":"2015-04-01T06:52:16Z","timestamp":1427871136000},"page":"62-72","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":91,"title":["Fibronectin type III domain containing 5 expression in skeletal muscle in chronic heart failure\u2014relevance of inflammatory cytokines"],"prefix":"10.1002","volume":"6","author":[{"given":"Yae","family":"Matsuo","sequence":"first","affiliation":[{"name":"Department of Cardiology University Leipzig \u2013 Heart Center Leipzig Leipzig Germany"},{"name":"Department of Cardiology Gunma University School of Medicine Maebashi 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