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

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.

• Authors: 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
• Journal: Journal of inflammation (London, England) (J Inflamm (Lond)) Vol. 16 Pg. 17 ( 2019) ISSN: 1476-9255 [Print] England
• PMID: 31312114 (Publication Type: Journal Article)