Deficiency of fibroblast growth factor 21 aggravates obesity-induced atrophic responses in skeletal muscle

Chu-Sook Kim; Yeonsoo Joe; Hye-Seon Choi; Sung Hoon Back; Jeong Woo Park; Hun Taeg Chung; Eun Roh; Min-Seon Kim; Tae Youl Ha; Rina Yu

doi:10.1186/s12950-019-0221-3

Deficiency of fibroblast growth factor 21 aggravates obesity-induced atrophic responses in skeletal muscle

J Inflamm (Lond). 2019 Jul 4:16:17. doi: 10.1186/s12950-019-0221-3. eCollection 2019.

Authors

Affiliations

¹ 1Department of Food Science and Nutrition, University of Ulsan, Ulsan, 44610 South Korea.
² 2Department of Biological Science, University of Ulsan, Ulsan, 44610 South Korea.
³ 3Appetite Regulation Laboratory, Asan Institute for Life Sciences, University of Ulsan College of Medicine, Seoul, 05505 South Korea.
⁴ 4Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Ulsan College of Medicine, Seoul, 05505 South Korea.
⁵ 5Research Group of Nutrition and Metabolic System, Korea Food Research Institute, Wanju, 55365 South Korea.

Abstract

Background: Obesity-induced skeletal muscle inflammation is a major contributor of skeletal muscle loss/atrophy and is implicated in metabolic complications such as insulin resistance. Fibroblast growth factor 21 (FGF21) is known to be an important metabolic regulator with anti-inflammatory properties. However, the effect of FGF21 on skeletal muscle atrophy is unclear. In this study, we investigated the effect of FGF21 deficiency on obesity-induced skeletal muscle inflammation and atrophy in mice.

Results: The expression of atrophic factors (MuRF1 and Atrogin-1) was upregulated at the mRNA and/or protein levels in the skeletal muscle of FGF21-deficient obese mice compared with wild type obese control mice. This was accompanied by an increase in levels of inflammatory cytokines (TNFα and MCP-1) and a reduction in AMPK phosphorylation. FGF21 treatment markedly suppressed TNFα-mediated inflammatory and atrophic responses in cultured myotubes, and the actions of FGF21 were blunted by the AMPK inhibitor compound C.

Conclusion: These findings suggest that FGF21 deficiency aggravates obesity-induced inflammation and atrophic responses in the skeletal muscle of obese mice, and FGF21 may protect inflammation-mediated atrophy through the AMPK pathway.

Keywords: Atrophy; Fibroblast growth factor 21; Inflammation; Muscle; Obesity.