Fibroblast growth factor 19 regulates skeletal muscle mass and ameliorates muscle wasting in mice
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.
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Administration of FGF19 promoted muscle hypertrophy and increased grip strength without AKT activation but with ERK stimulation.
“It has been recently reported that administration of FGF19 promoted muscle hypertrophy and increased grip strength without AKT activation but with ERK stimulation26.”
From Mechanisms of muscle atrophy and hypertrophy: implications in health and disease (2021) · cites this paper as [26]
Injecting mice daily with exogenous FGF19 increased skeletal muscle mass and strength.
“Injecting mice daily with exogenous FGF19, a closely related endocrine FGF member produced in the gut, increased skeletal muscle mass and strength.”
From Fibroblast growth factor 21 controls mitophagy and muscle mass (2019) · cites this paper as [22]
Skeletal muscle hypertrophy effects were not elicited by administering FGF21.
“Remarkably, the skeletal muscle hypertrophy effects were not elicited by administrating FGF21.22”
From Fibroblast growth factor 21 controls mitophagy and muscle mass (2019) · cites this paper as [22]
KLB expression is primarily restricted to specific metabolic tissues (liver, pancreas, adipose) and lower in brain; KLB is not expressed in muscle.
“KLB expression is primarily restricted to specific metabolic tissues (for example, the liver, pancreas and adipose tissue)5, and lower expression is observed in the brain22,48–50. Despite some reports to the contrary51,52, KLB is not expressed in muscle5,41.”
From Metabolic messengers: FGF21 (2021) · cites this paper as [52]
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- Authors
- Benoit, B., Meugnier, E., Castelli, M., Chanon, S., Vieille-Marchiset, A., Durand, C., Bendridi, N., Pesenti, S., Monternier, P.-A., Durieux, A.-C., Freyssenet, D., Rieusset, J., Lefai, E., Vidal, H., & Ruzzin, J.
- Affiliations
- University of Bergen (NO)
- Lyon 1 Université (FR)
- Laboratoire Interuniversitaire de Biologie de la Motricité (FR)
- Corresponding author
- Ruzzin, Jérôme
- ORCID
- Venue
- Nature Medicine
- Published
- 2017-06-26
- Volume
- 23
- Issue
- 8
- Pages
- 990-996
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W2648229824
- Cited by
- 225
- References
- 36
- Citations by year
- 2026: 19 · 2025: 18 · 2024: 29 · 2023: 26 · 2022: 29 · 2021: 31 · 2020: 24 · 2019: 21 · 2018: 24 · 2017: 3
- FWCI
- 8.04
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
- Keywords
- FGF19, skeletal muscle mass, muscle atrophy, muscle hypertrophy, muscle fiber size, ERK signaling, S6K1, mTOR signaling, β-Klotho, glucocorticoid-induced muscle atrophy, sarcopenia, FGF21
- MeSH terms
- Klotho Proteins, Animals, Fibroblast Growth Factors, Glucocorticoids, Humans, Immunohistochemistry, Membrane Proteins, Muscular Atrophy, Obesity, Organ Size, Recombinant Proteins, Blotting, Western, Mice, Knockout, Muscle, Skeletal, Muscle Fibers, Skeletal, Hand Strength, Immunoprecipitation, Cell Size, Mice, Sarcopenia, Transcriptome, In Vitro Techniques
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