Treatment with fibroblast growth factor 19 increases skeletal muscle fiber size, ameliorates metabolic perturbations and hepatic inflammation in 5/6 nephrectomized mice.

Abstract

Chronic kidney disease (CKD) is associated with osteosarcopenia, and because a physical decline in patients correlates with an increased risk of morbidity, an improvement of the musculoskeletal system is expected to improve morbi-mortality. We recently uncovered that the intestinal hormone Fibroblast Growth Factor 19 (FGF19) is able to promote skeletal muscle mass and strength in rodent models, in addition to its capacity to improve glucose homeostasis. Here, we tested the effects of a treatment with recombinant human FGF19 in a CKD mouse model, which associates sarcopenia and metabolic disorders. In 5/6 nephrectomized (5/6Nx) mice, subcutaneous FGF19 injection (0.1 mg/kg) during 18 days increased skeletal muscle fiber size independently of food intake and weight gain, associated with decreased gene expression of myostatin. Furthermore, FGF19 treatment attenuated glucose intolerance and reduced hepatic expression of gluconeogenic genes in uremic mice. Importantly, the treatment also decreased gene expression of liver inflammatory markers in CKD mice. Therefore, our results suggest that FGF19 may represent a novel interesting therapeutic strategy for a global improvement of sarcopenia and metabolic complications in CKD.

• Authors: Berengère Benoit, Alice Beau, Émilie Bres, Stéphanie Chanon, Claudie Pinteur, Aurélie Vieille-Marchiset, Audrey Jalabert, Hao Zhang, Priyanka Garg, Maura Strigini, Laurence Vico, Jérôme Ruzzin, Hubert Vidal, Laetitia Koppe
• Journal: Scientific reports (Sci Rep) Vol. 13 Issue 1 Pg. 5520 (04 04 2023) ISSN: 2045-2322 [Electronic] England
• PMID: 37015932 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2023. The Author(s).

Chemical References

• Fibroblast Growth Factors

Topics

• Animals
• Humans
• Mice
• Fibroblast Growth Factors (pharmacology)
• Inflammation (pathology)
• Muscle Fibers, Skeletal (metabolism)
• Muscle, Skeletal (metabolism)
• Renal Insufficiency, Chronic (complications)
• Sarcopenia (pathology)