FGF19 protects skeletal muscle against obesity-induced muscle atrophy, metabolic derangement and abnormal irisin levels via the AMPK/SIRT-1/PGC-α pathway.

Abstract

Obesity is associated with biological dysfunction in skeletal muscle. As a condition of obesity accompanied by muscle mass loss and physical dysfunction, sarcopenic obesity (SO) has become a novel public health problem. Human fibroblast growth factor 19 (FGF19) plays a therapeutic role in metabolic diseases. However, the protective effects of FGF19 on skeletal muscle in obesity and SO are still not completely understood. Our results showed that FGF19 administration improved muscle loss and grip strength in young and aged mice fed a high-fat diet (HFD). Increases in muscle atrophy markers (FOXO-3, Atrogin-1, MuRF-1) were abrogated by FGF19 in palmitic acid (PA)-treated C2C12 myotubes and in the skeletal muscle of HFD-fed mice. FGF19 not only reduced HFD-induced body weight gain, excessive lipid accumulation and hyperlipidaemia but also promoted energy expenditure (PGC-1α, UCP-1, PPAR-γ) in brown adipose tissue (BAT). FGF19 treatment restored PA- and HFD-induced hyperglycaemia, impaired glucose tolerance and insulin resistance (IRS-1, GLUT-4) and mitigated the PA- and HFD-induced decrease in FNDC-5/irisin expression. However, these beneficial effects of FGF19 on skeletal muscle were abolished by inhibiting AMPK, SIRT-1 and PGC-1α expression. Taken together, this study suggests that FGF19 protects skeletal muscle against obesity-induced muscle atrophy, metabolic derangement and abnormal irisin secretion partially through the AMPK/SIRT-1/PGC-α signalling pathway, which might be a potential therapeutic target for obesity and SO.

• Authors: Ai Guo, Kai Li, Hong-Chuan Tian, Zhen Fan, Qiu-Nan Chen, Yun-Fei Yang, Jing Yu, Yong-Xin Wu, Qian Xiao
• Journal: Journal of cellular and molecular medicine (J Cell Mol Med) Vol. 25 Issue 7 Pg. 3585-3600 (04 2021) ISSN: 1582-4934 [Electronic] England
• PMID: 33751819 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.

Chemical References

• FGF19 protein, human
• FNDC5 protein, mouse
• Fibronectins
• Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
• Ppargc1a protein, mouse
• Fibroblast Growth Factors
• AMP-Activated Protein Kinases
• Sirtuin 1

Topics

• AMP-Activated Protein Kinases (metabolism)
• Adipose Tissue, Brown (drug effects)
• Animals
• Cell Line
• Diet, High-Fat
• Fibroblast Growth Factors (pharmacology, physiology)
• Fibronectins (metabolism)
• Hyperglycemia (metabolism)
• Hyperlipidemias (metabolism)
• Insulin Resistance
• Lipid Metabolism (drug effects)
• Male
• Mice
• Mice, Inbred C57BL
• Muscle Fibers, Skeletal (metabolism)
• Muscle, Skeletal (drug effects, metabolism)
• Muscular Atrophy (metabolism)
• Obesity (metabolism)
• Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha (metabolism)
• Signal Transduction
• Sirtuin 1 (metabolism)