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Fibroblast growth factor 19 regulates skeletal muscle mass and ameliorates muscle wasting in mice.
Nature Medicine ( IF 82.9 ) Pub Date : 2017-Aug-01 , DOI: 10.1038/nm.4363
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 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.

中文翻译:

成纤维细胞生长因子19调节骨骼肌质量并改善小鼠的肌肉消耗。

内分泌源性激素成纤维细胞生长因子(FGF)19最近已成为治疗代谢性疾病的潜在靶标。鉴于骨骼肌是关键的代谢器官,我们探讨了FGF19在该组织中的作用。在这里,我们报道了FGF19在通过增加肌肉纤维大小来调节骨骼肌质量以及保护肌肉免受萎缩方面的新型功能。FGF19的治疗可引起小鼠骨骼肌肥大,而FGF19的生理和药理剂量则在体外显着增加了人类肌管的大小。FGF21是一种密切相关的内分泌FGF成员,并未引起这些作用。无论在体内还是体外,FGF19都能刺激细胞外信号调节蛋白激酶1/2(ERK1 / 2)和核糖体蛋白S6激酶(S6K1)的磷酸化,mTOR依赖的肌肉细胞生长调节剂。此外,具有骨骼肌特异性遗传缺陷的β-Klotho(KLB)(FGF15 / 19的专职共受体)小鼠(参考文献2,3)对FGF19的肥大作用无反应。最后,在小鼠中,FGF19改善了糖皮质激素治疗或肥胖以及少肌症所引起的骨骼肌萎缩。综上所述,这些发现提供了证据,证明肠激酶FGF19是调节骨骼肌质量的新因素,并且具有治疗肌肉萎缩的治疗潜力。FGF19改善了糖皮质激素治疗或肥胖引起的骨骼肌萎缩以及肌肉减少症。综上所述,这些发现提供了证据,证明肠激酶FGF19是调节骨骼肌质量的新因素,并且具有治疗肌肉萎缩的治疗潜力。FGF19改善了糖皮质激素治疗或肥胖引起的骨骼肌萎缩以及肌肉减少症。综上所述,这些发现提供了证据,证明肠激酶FGF19是调节骨骼肌质量的新因素,并且具有治疗肌肉萎缩的治疗潜力。
更新日期:2017-09-07
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