Elevated meteorin-like protein from high-intensity interval training improves heartfunctionviaAMPK/HDAC4pathway  

作　　者：Yongshun Wang Jie Yuan Huadong Liu Jie Chen Jieru Zou Xiaoyi Zeng Lei Du Xin Sun Zhengyuan Xia Qingshan Geng Yin Cai Jingjin Liu 

机构地区：[1]Department of Cardiology,Shenzhen People's Hospital(The Second Clinical Medical College,Jinan University,The First Affiliated Hospital,Southern University of Science and Technology),Shenzhen,Guangdong 518020,China [2]Shenzhen Clinical Research Center for Geriatrics,Shenzhen People's Hospital,Shenzhen,Guangdong 518020,China [3]Department of Anesthesiology,Affiliated Hospital of Guangdong Medical University,Zhanjiang,Guangdong 524001,China [4]Faculty of Chinese Medicine,State Key Laboratory of Quality Research in Chinese Medicine,Macao University of Science and Technology,Taipa,Macao 999078,China [5]Department of Health Technology and Informatics,The Hong Kong Polytechnic University,Kowloon,Hong Kong 999077,China

出　　处：《Genes & Diseases》2024年第6期409-424,共16页基因与疾病（英文）

基　　金：supported by the National Natural Science Foundation of China (No.82200315);Guangdong Basic and Applied Basic Research Foundation of China (No.2021A1515111145);Sanming Project of Medicine in Shenzhen,Guangdong,China (No.SzSM201412012);Scienceand Technology Planning Project of Shenzhen Municipality,Guangdong,China (No.JCYJ20210324113807021,JCYJ20210324113614038);Major scientificresearchproject of Shenzhen People's Hospital (China) (No.sYWGSJCYJ202301);Life Science Research Start-up Fund of PolyU SZRI (China) (No.I2021A008).

摘　　要：High-intensity interval training(HIlT)has been found to be more effective in relieving heart failure(HF)symptoms,than moderate-intensity continuous aerobic training(MICT).Additionally,higher meteorin-like protein(Metrnl)levels are seen after HIIT versus MICT.We investigated whether Metrnl contributed to post-HF cardiac functional improve-ments,and the signaling pathways involved.50 HF patients underwent MICT,and another 50,HllT,which was followed by cardiac function and serum Metrnl measurements.Metrnl was also measured in both blood and skeletal muscle samples of mice with transverse aortic constriction-induced HF after undergoing HIIT.Afterward,shRNA-containing adenovectors were injected into mice,yielding five groups:control,HF,HF+HIIT+scrambled shRNA,HF+HIIT+shMetrnl,and HF+Metrnl(HF+exogenous Metrnl).Mass spectrometry identified specific signaling pathways associated with increased Metrnl,which was confirmed with biochemical analyses.Glucose metabolism and mitochondrial functioning were evaluated in cardiomyocytes from the five groups.Both HF patients and mice had higher circulating Metrnl levels post-HIIT.Metrnl activated AMPK in cardiomyocytes,subsequently increasing histone deacetylase 4(HDAC4)phosphorylation,leading to its cytosolic sequestration and inactivation via binding with chaperone protein 14-3-3.HDAC4 inactivation removed its repression on glucose transporter type 4,which,along with increased mitochondrial complex I-V expression,yielded improved aerobic glucose respiration and alleviation of mitochondrial dysfunction.All these changes ultimately result in improved post-HF cardiac functioning.HIT increased skeletal muscle Metrnl production,which then operated on HF hearts to alleviate their functional defects,via increasing aerobic glucose metabolism through AMPK-HDAC4 signaling.

关 键 词：AMPK GLUT4 HDAC4 Heart failure High intensity interval training 

分 类 号：R541[医药卫生—心血管疾病]