Fibroblast growth factor 19 regulates skeletal muscle mass and ameliorates muscle wasting in mice

Nature Medicine 23, 990 (2017). doi:10.1038/nm.4363 Authors: Bérengère Benoit, Emmanuelle Meugnier, Martina Castelli, Stéphanie Chanon, Aurélie Vieille-Marchiset, Christine Durand, Nadia Bendridi, Sandra Pesenti, Pierre-Axel Monternier, Anne-Cécile Durieux, Damien Freyssenet, Jennifer Rieusset, Etienne Lefai, Hubert Vidal & Jérôme Ruzzin The endocrine-derived hormone fibroblast growth factor (FGF) 19 has recently emerged as a potential target for treating metabolic disease. Given that skeletal muscle is a key metabolic organ, we explored the role of FGF19 in that tissue. Here we report a novel function of FGF19 in regulating skeletal muscle mass through enlargement of muscle fiber size, and in protecting muscle from atrophy. Treatment with FGF19 causes skeletal muscle hypertrophy in mice, while physiological and pharmacological doses of FGF19 substantially increase the size of human myotubes in vitro. These effects were not elicited by FGF21, a closely related endocrine FGF member. Both in vitro and in vivo, FGF19 stimulates the phosphorylation of the extracellular-signal-regulated protein kinase 1/2 (ERK1/2) and the ribosomal protein S6 kinase (S6K1), an mTOR-dependent master regulator of muscle cell growth. Moreover, mice with a skeletal-muscle-specific genetic deficiency of β-Klotho (KLB), an obligate co-receptor for FGF15/19 (refs. 2,3), were unresponsive to the hypertrophic effect of FGF19. Finally, in mice, FGF19 ameli...
Source: Nature Medicine - Category: General Medicine Authors: Tags: Letter Source Type: research