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

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

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.

FIBROBLAST growth factors; SKELETAL muscle; MYOSITIS; INSULIN resistance

Journal of Inflammation, 2019, Vol 16, Issue 1, pN.PAG

1476-9255

Academic Journal

10.1186/s12950-019-0221-3