journal article·2020-10Open access

IRF4 in Skeletal Muscle Regulates Exercise Capacity via PTG/Glycogen Pathway

Xiaopeng Zhu, Ting Yao, Ru Wang, Shanshan Guo, Xin Wang, Zhenqi Zhou, Yan Zhang, Xiaozhen Zhuo, Ruitao Wang, John Zhong Li, Tiemin Liu, Xingxing Kong

Advanced Science· Volume 7· Issue 19

Abstract

Abstract 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.
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Research context

OpenAlex topics: Adipose Tissue and Metabolism · Muscle metabolism and nutrition · Exercise and Physiological Responses

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Division of Pediatric Endocrinology Department of Pediatrics UCLA Children's Discovery and Innovation Institute David Geffen School of Medicine at UCLA Los Angeles CA 90095 USA

Department of Endocrinology and Metabolism Zhongshan Hospital Fudan University Shanghai 200032 P. R. China

Fudan Institute for Metabolic Disease Fudan University Shanghai 200032 P. R. China

School of Kinesiology Key Laboratory of Exercise and Health Sciences of Ministry of Education Shanghai University of Sport Shanghai 200438 P. R. China

Department of Internal Medicine Harbin Medical University Cancer Hospital Harbin Medical University No. 150 Haping ST, Nangang District Harbin Heilongjiang 150081 P. R. China

Department of Medicine Division of Endocrinology, Diabetes and Hypertension David Geffen School of Medicine University of California Los Angeles CA 90095 USA

School of Life Sciences Fudan University Shanghai 200032 P. R. China

Department of Cardiology The First Affiliated Hospital Xi'an Jiaotong University Xi'an Shanxi 710061 P. R. China

The Key Laboratory of Rare Metabolic Disease Department of Biochemistry and Molecular Biology The Key Laboratory of Human Functional Genomics of Jiangsu Province Nanjing Medical University Nanjing Jiangsu 211166 P. R. China

State Key Laboratory of Genetic Engineering Department of Endocrinology and Metabolism and School of Life Sciences Zhongshan Hospital Fudan University Shanghai 200032 P. R. China

Institute of Metabolism and Integrative Biology and Collaborative Innovation Center for Genetics and Development Fudan University Shanghai 200032 P. R. China

Human Phenome Institute Fudan University Shanghai 200032 P. R. China

Funding

University of California, Los Angeles · American Heart Association · China Scholarship Council · National Institutes of Health

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