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Nat Med. 2017 Aug;23(8):990-996. doi: 10.1038/nm.4363. Epub 2017 Jun 26.

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

Author information

1
Department of Biology, University of Bergen, Bergen, Norway.
2
Univ-Lyon, CarMeN Laboratory, INSERM 1060, INRA 1397, Université Claude Bernard Lyon1, INSA Lyon, Oullins, France.
3
Univ-Lyon, Laboratoire Interuniversitaire de Biologie de la Motricité, EA7424, Université Jean Monnet, Saint Etienne, France.

Abstract

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 ameliorates skeletal muscle atrophy induced by glucocorticoid treatment or obesity, as well as sarcopenia. Taken together, these findings provide evidence that the enterokine FGF19 is a novel factor in the regulation of skeletal muscle mass, and that it has therapeutic potential for the treatment of muscle wasting.

Comment in

PMID:
28650457
DOI:
10.1038/nm.4363
[Indexed for MEDLINE]

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