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Muscle disorders

FGF19 reduces muscle wasting

Nature Reviews Drug Discovery volume 16, pages 528–529 (2017)Cite this article

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FGF19 had previously been shown to increase energy expenditure, reduce fat mass, and improve lipid and glucose homeostasis in mouse models. The authors postulated that these effects could be mediated through the largest insulin target tissue in the body: skeletal muscle. They found that mice injected daily with recombinant human FGF19 for 7 days had higher skeletal muscle mass and better strength than did vehicle-treated mice. The muscles in these mice also showed a shift towards containing larger myofibers. The receptors for FGF19 in mice— FGFR1, FGFR4 and β-klotho — are expressed in skeletal muscle, suggesting that FGF19 could act through these receptor complexes in this tissue. In support of this hypothesis, FGF19 treatment had no effect on muscle mass in mice with a muscle-specific deletion of Klb, which encodes β-klotho.

Recombinant FGF19 increased the myotube area in primary human muscle cells undergoing differentiation from myoblasts to myotubes, as well as in fully differentiated myotubes. In terms of signalling, FGF19 increased the phosphorylation of ERK1/2 and of the downstream ERK1/2 targets p90 ribosomal S6 kinase (p90RSK) and tuberin. FGF19 also increased the activity of mTOR, as measured by phosphorylation of its downstream target S6 kinase (S6K). Treatment of cells with U0126, which inhibits phosphorylation of ERK1/2, or with the mTOR inhibitor PP242 decreased the FGF19-induced hypertrophy.

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References

  1. Benoit, B. et al. Fibroblast growth factor 19 regulates skeletal muscle mass and ameliorates muscle wasting in mice. Nat. Med. http://dx.doi.org/10.1038/nm.4363 (2017)

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  1. Megan Cully
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Degirolamo, C., Sabbà, C. & Moschetta, A. Therapeutic potential of the endocrine fibroblast growth factors FGF19, FGF21 and FGF23. Nat. Rev. Drug Discov. 15, 51–69 (2016)

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Cully, M. FGF19 reduces muscle wasting. Nat Rev Drug Discov 16, 528–529 (2017). https://doi.org/10.1038/nrd.2017.132

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