title: Fibroblast Growth Factor 21 (FGF21) Promotes Formation of Aerobic Myofibers via the FGF21-SIRT1-AMPK-PGC1α Pathway.
abstract: Fibroblast growth factor 21(FGF21) is a pivotal regulator of energy metabolism, which is currently being assessed as a potential drug target for the treatment of insulin-resistant conditions. However, the cellular mechanisms by which FGF21 affects myogenesis remain unclear. In this study, we explored the function of FGF21 in myogenesis both in vitro and in vivo. Our experiments showed for the first time that FGF21 promotes myoblast differentiation and serves as a switch of molecular transformation from anaerobic myofibers to aerobic myofibers via the FGF21-SIRT1-AMPK-PGC1α axis. Furthermore, we employed the Dual-Luciferase Reporter Assay System and Electrophoretic Mobility Shift Assay (EMSA) and demonstrated that MYOD, a major myogenic transcription factor, binds directly to the promoter region of Fgf21, leading to the activation of Fgf21 expression in mouse C2C12 myoblasts. Our study revealed a novel mechanism of myogenesis and muscle fiber transformation and indicated that FGF21 serves as a vital regulator of muscle development and important contributor to the pathogenesis of myopathy. J. Cell. Physiol. 232: 1893-1906, 2017. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of the Ministry of Education and Key Laboratory of Swine Genetics and Breeding of the Ministry of Agriculture, Huazhong Agricultural University, Wuhan, Hubei, P. R. China.
authors.forename: Xinyi
authors.initials: X
authors.lastname: Liu
authors.affiliation: Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of the Ministry of Education and Key Laboratory of Swine Genetics and Breeding of the Ministry of Agriculture, Huazhong Agricultural University, Wuhan, Hubei, P. R. China.
authors.forename: Yongliang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of the Ministry of Education and Key Laboratory of Swine Genetics and Breeding of the Ministry of Agriculture, Huazhong Agricultural University, Wuhan, Hubei, P. R. China.
authors.forename: Liming
authors.initials: L
authors.lastname: Hou
authors.affiliation: Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of the Ministry of Education and Key Laboratory of Swine Genetics and Breeding of the Ministry of Agriculture, Huazhong Agricultural University, Wuhan, Hubei, P. R. China.
authors.forename: Yuanzhu
authors.initials: Y
authors.lastname: Xiong
authors.affiliation: Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of the Ministry of Education and Key Laboratory of Swine Genetics and Breeding of the Ministry of Agriculture, Huazhong Agricultural University, Wuhan, Hubei, P. R. China.|The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, Hubei, P. R. China.
authors.forename: Shuhong
authors.initials: S
authors.lastname: Zhao
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000332:Aerobiosis; D000818:Animals; D001483:Base Sequence; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D004734:Energy Metabolism / Q000235:genetics; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D024510:Muscle Development / Q000235:genetics; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D017570:MyoD Protein / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D056564:Sirtuin 1 / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D017570:MyoD Protein; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors; D055372:AMP-Activated Protein Kinases; D056564:Sirtuin 1