BMAL1/PGC1α4-FNDC5/irisin axis impacts distinct outcomes of time-of-day resistance exercise  

作　　者：Mingwei Guo Fei Shen Xiaozhen Guo Jun Zhang Ying Ma Xia Wu Hui Zuo Jing Yao Yepeng Hu Dongmei Wang Yu Li Jin Li Jin Qiu Jian Yu Meiyao Meng Ying Zheng Xin Chen Mingkai Gong Kailin Liu Ling Jin Xiangyu Ren Qiang Zhang Yu Zhao Xuejiang Gu Feixia Shen Dali Li Liangcai Gao Chang Liu Fei Zhou Mian Li Jiqiu Wang Shuzhe Ding Xinran Ma Jian Lu Cen Xie Junjie Xiao Lingyan Xu 

机构地区：[1]Shanghai Key Laboratory of Regulatory Biology,Institute of Biomedical Sciences and School of Life Sciences,East China Normal University,Shanghai 200241,China [2]Key Laboratory of Adolescent Health Assessment and Exercise Intervention of Ministry of Education,College of Physical Education and Health,East China Normal University,Shanghai 200241,China [3]Institute of Physical Education,Jiangsu Normal University,Xuzhou 221116,China [4]State Key Laboratory of Drug Research,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai 201203,China [5]Department of Endocrine and Metabolic Diseases,the First Affiliated Hospital of Wenzhou Medical University,Wenzhou 325000,China [6]Cardiac Regeneration and Ageing Lab,Institute of Cardiovascular Sciences,School of Life Science,Shanghai University,Shanghai 200444,China [7]State Key Laboratory of Natural Medicines,China Pharmaceutical University,Nanjing 211198,China [8]Cambridge-Suda Genomic Resource Center,Medical College of Soochow University,Suzhou 215123,China [9]Department of Endocrinology and Metabolism,China National Research Center for Metabolic Diseases,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200025,China

出　　处：《Journal of Sport and Health Science》2025年第1期107-129,共23页运动与健康科学(英文)

基　　金：supported by funds from National Key Research and Development Program of China (2019YFA0904500 to LX, 2023YFA1800400 to LX, and 2018YFE0113500 to JX);the National Natural Science Foundation of China (82301777 to MG, 32222024 to LX, 32325024 to XM, 32071148 to LX, and 91957116 to CX);Fundamental Research Funds for the Central Universities, Science and Technology Commission of Shanghai Municipality (21140904300 to XM and 22ZR1421200 to LX);Innovation Program of Shanghai Municipal Education Commission (2017-01-07-00-09-E00042 to JX);Key Project of 2022 Higher Education Scientific Research Planning Project of China Association of Higher Education (22TY0218 to FS);Youth Fund for Humanities and Social Sciences Research of the Ministry of Education (22YJC890023 to FS);Postdoctoral Fellowship Program of CPSF (GZB20230219 to MG);China Postdoctoral Science Foundation (2023M741183 to MG);ECNU public platform for Innovation (011).

摘　　要：Background: Resistance exercise leads to improved muscle function and metabolic homeostasis.Yet how circadian rhythm impacts exercise outcomes and its molecular transduction remains elusive.Methods: Human volunteers were subjected to 4 weeks of resistance training protocols at different times of day to assess training outcomes and their associations with myokine irisin.Based on rhythmicity of Fibronectin type III domain containing 5(FNDC5/irisin),we trained wild type and FNDC5 knockout mice at late active phase(high FNDC5/irisin level)or late rest phase(low FNDC5/irisin level)to analyze exercise benefits on muscle function and metabolic homeostasis.Molecular analysis was performed to understand the regulatory mechanisms of FNDC5 rhythmicity and downstream signaling transduction in skeletal muscle.Results: In this study,we showed that regular resistance exercises performed at different times of day resulted in distinct training outcomes in humans,including exercise benefits and altered plasma metabolomics.We found that muscle FNDC5/irisin levels exhibit rhythmicity.Consistent with human data,compared to late rest phase(low irisin level),mice trained chronically at late active phase(high irisin level)gained more muscle capacity along with improved metabolic fitness and metabolomics/lipidomics profiles under a high-fat diet,whereas these differences were lost in FNDC5 knockout mice.Mechanistically,Basic helix-loop-helix ARNT like 1(BMAL1)and Peroxisome proliferative activated receptor,gamma,coactivator 1 alpha 4(PGC1α4)induce FNDC5/irisin transcription and rhythmicity,and the signaling is transduced viaαV integrin in muscle.Conclusion: Together,our results offered novel insights that exercise performed at distinct times of day determines training outcomes and metabolic benefits through the rhythmic regulation of the BMAL1/PGC1α4-FNDC5/irisin axis.

关 键 词：Daily variance CIRCADIAN Muscle strength Metabolic benefits Resistance exercise 

分 类 号：R87[医药卫生—运动医学]