Open AccessIRF4 in Skeletal Muscle Regulates Exercise Capacity via PTG/Glycogen Pathway
Author(s) -
Zhu Xiaopeng,
Yao Ting,
Wang Ru,
Guo Shanshan,
Wang Xin,
Zhou Zhenqi,
Zhang Yan,
Zhuo Xiaozhen,
Wang Ruitao,
Li John Zhong,
Liu Tiemin,
Kong Xingxing
Publication year - 2020
Publication title -
advanced science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.388
H-Index - 100
ISSN - 2198-3844
DOI - 10.1002/advs.202001502
Subject(s) - glycogen , skeletal muscle , endocrinology , medicine , glycogen synthase , irf4 , gene knockdown , glycogen debranching enzyme , chemistry , biology , biochemistry , transcription factor , apoptosis , gene
Exercise‐induced fatigue and exhaustion are interesting areas for many researchers. Muscle glycogen is critical for physical performance. However, how glycogen metabolism is manipulated during exercise is not very clear. The aim here is to assess the impact of interferon regulatory factor 4 (IRF4) on skeletal muscle glycogen and subsequent regulation of exercise capacity. Skeletal muscle‐specific IRF4 knockout mice show normal body weight and insulin sensitivity, but better exercise capacity and increased glycogen content with unaltered triglyceride levels compared to control mice on chow diet. In contrast, mice overexpression of IRF4 displays decreased exercise capacity and lower glycogen content. Mechanistically, IRF4 regulates glycogen‐associated regulatory subunit protein targeting to glycogen (PTG) to manipulate glucose metabolism in skeletal muscle. Knockdown of PTG can reverse the effects imposed by the absence of IRF4 in vivo. These studies reveal a regulatory pathway including IRF4/PTG/glycogen synthesis on controlling exercise capacity.