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

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IRF4 in Skeletal Muscle Regulates Exercise Capacity via PTG/Glycogen Pathway
Advanced Science ( IF 14.3 ) Pub Date : 2020-08-01 , DOI: 10.1002/advs.202001502
Xiaopeng Zhu _{1,

2,

3} , Ting Yao ₁ , Ru Wang ₄ , Shanshan Guo ₄ , Xin Wang _{1,

5} , Zhenqi Zhou ₆ , Yan Zhang ₇ , Xiaozhen Zhuo ₈ , Ruitao Wang ₅ , John Zhong Li ₉ , Tiemin Liu _{10,

11,

12} , Xingxing Kong ₁

Affiliation

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.

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.

中文翻译：

骨骼肌中的 IRF4 通过 PTG/糖原途径调节运动能力

运动引起的疲劳和疲惫是许多研究人员感兴趣的领域。肌糖原对于身体表现至关重要。然而，运动过程中如何控制糖原代谢尚不清楚。此处的目的是评估干扰素调节因子 4 (IRF4) 对骨骼肌糖原以及随后运动能力调节的影响。与普通饮食的对照小鼠相比，骨骼肌特异性 IRF4 敲除小鼠表现出正常的体重和胰岛素敏感性，但运动能力更好，糖原含量增加，甘油三酯水平不变。相反，IRF4过度表达的小鼠表现出运动能力下降和糖原含量降低。从机制上讲，IRF4 调节靶向糖原 (PTG) 的糖原相关调节亚基蛋白，以操纵骨骼肌中的葡萄糖代谢。 PTG 的敲低可以逆转体内 IRF4 缺失所带来的影响。这些研究揭示了控制运动能力的调节途径，包括 IRF4/PTG/糖原合成。

更新日期：2020-10-07

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