Endocrine Protection of Ischemic Myocardium by FGF21 from the Liver and Adipose Tissue

• Published in: Scientific reports 2013-09, Vol.3 (1), p.2767-2767, Article 2767
• Main Authors: Liu, Shu Q., Roberts, Derek, Kharitonenkov, Alexei, Zhang, Brian, Hanson, Samuel M., Li, Yan Chun, Zhang, Li-Qun, Wu, Yu H.
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; 631/337; 631/443; 631/553; 631/80; Adipocytes; Adipose tissue; Adipose Tissue - metabolism; Adipose Tissue - pathology; Adipose Tissue - physiopathology; AKT1 protein; Animals; bcl-Associated Death Protein - metabolism; Cardiomyocytes; Cardiotonic Agents - metabolism; Caspase; Caspase 3 - metabolism; Caspase-3; Cell death; Endocrine System - metabolism; Endocrine System - pathology; Fibroblast growth factor receptor 1; Fibroblast Growth Factors - metabolism; Gene Silencing; Glucuronidase; Heart Function Tests; Heart Ventricles - metabolism; Heart Ventricles - pathology; Heart Ventricles - physiopathology; Hemodynamics; Humanities and Social Sciences; Ischemia; Klotho protein; Liver; Liver - metabolism; Liver - pathology; Liver - physiopathology; Membrane proteins; Mice; multidisciplinary; Myocardial infarction; Myocardial ischemia; Myocardial Ischemia - enzymology; Myocardial Ischemia - pathology; Myocardial Ischemia - physiopathology; Myocardial Ischemia - prevention & control; Myocardial Reperfusion Injury - enzymology; Myocardial Reperfusion Injury - pathology; Myocardial Reperfusion Injury - physiopathology; Myocardium; Myocytes, Cardiac - enzymology; Myocytes, Cardiac - pathology; Phosphatidylinositol 3-Kinases; Phosphorylation; Protein Binding; Proto-Oncogene Proteins c-akt - metabolism; Receptor, Fibroblast Growth Factor, Type 1 - metabolism; Reperfusion; RNA, Small Interfering - metabolism; Rodents; Science; Signal Transduction; Up-Regulation
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep02767

Myocardial ischemia, while causing cardiomyocyte injury, can activate innate protective processes, enhancing myocardial tolerance to ischemia. Such processes are present in not only the heart, but also remote organs. In this investigation, we demonstrated a cardioprotective process involving FGF21 from the liver and adipose tissue. In response to myocardial ischemia/reperfusion injury in the mouse, FGF21 was upregulated and released from the hepatic cells and adipocytes into the circulation and interacted with FGFR1 in cardiomyocytes under the mediation of the cell membrane protein β-Klotho, inducing FGFR1 phosphorylation. This action caused phosphorylation of the signaling molecules PI3K p85, Akt1 and BAD, thereby reducing caspase 3 activity, cell death and myocardial infarction in association with improvement of myocardial function. These observations suggest that FGF21 is upregulated and released from the liver and adipose tissue in myocardial injury, contributing to myocardial protection by the mediation of the FGFR1/β-Klotho–PI3K–Akt1–BAD signaling network.