The Yin to FGF19's Yang

At left, FGF19.

By Emw - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=8767926

I recently wrote about the potential benefits of FGF19. However, in biology, many things are “double edged swords” and the same things that can promote useful growth in one context can, in another, promote cancer.  Abstract:

Fibroblast growth factors (FGFs) and their cognate receptors, FGF receptors (FGFRs), play critical roles in a variety of normal developmental and physiological processes. Numerous reports support a role for deregulation of FGF-FGFR signaling, whether it is at the ligand and/or receptor level, in tumor development and progression. The FGF19-FGFR4 signaling axis has been implicated in the pathogenesis of several cancers, including hepatocellular carcinomas in mice and potentially in humans. This chapter focuses on recent progress in the understanding of the molecular mechanisms of FGF19 action and its potential involvement in cancer.

This is why various cutting edge treatments must always take into account potential side effects. Now, of course, there is a difference between normal and deregulated FGF signaling and it may be possible to use FGFs in therapy responsibly: the point is that all possibilities, both positive and negative, need to be considered and evaluated.

FGF19 Against Muscle Wasting

https://i.ytimg.com/vi/uKMVIfas12k/hqdefault.jpg

Muscle wasting occurs in a variety of diseases as well as aging (sarcopenia). This study shows that a growth factor called FGF 19 increases muscle size in mice and increases human muscle cell size in culture.  In addition, mice with induced muscle wasted were helped by FGF19.  Therefore, this has possible clinical applications for various human disorders.  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