COVID-19 induces new-onset insulin resistance and lipid metabolic dysregulation via regulation of secreted metabolic factors  

作　　者：Xi He Chenshu Liu Jiangyun Peng Zilun Li Fang Li Jian Wang Ao Hu Meixiu Peng Kan Huang Dongxiao Fan Na Li Fuchun Zhang Weiping Cai Xinghua Tan Zhongwei Hu Xilong Deng Yueping Li Xiaoneng Mo Linghua Li Yaling Shi Li Yang Yuanyuan Zhu Yanrong Wu Huichao Liang Baolin Liao Wenxin Hong Ruiying He Jiaojiao Li Pengle Guo Youguang Zhuo Lingzhai Zhao Fengyu Hu Wenxue Li Wei Zhu Zefeng Zhang Zeling Guo Wei Zhang Xiqiang Hong Wei kang Cai Lei Gu Ziming Du Yang Zhang Jin Xu Tao Zuo Kai Deng Li Yan Xinwen Chen Sifan Chen Chunliang Lei 

机构地区：[1]Guangzhou Eighth People's Hospital,Guangzhou Medical University,Guangzhou,China [2]Division of Vascular Surgery,The First Affiliated Hospital of Sun Yat-sen University,Guangzhou,China [3]National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases,The First Affiliated Hospital of Sun Yat-sen University,Guangzhou,China [4]Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation,Guangdong-Hong Kong Joint Laboratory for RNA Medicine,Sun Yat-Sen Memorial Hospital,Sun Yat-Sen University,Guangzhou,China [5]Medical Research Center,Sun Yat-Sen Memorial Hospital,Sun Yat-Sen University,Guangzhou,China [6]Department of Obstetrics and Gynecology,Guangzhou Women and Children Medical Center,Guangzhou Medical University,Guangzhou,China [7]Institute of Human Virology,Key Laboratory of Tropical Disease Control of Ministry of Education,Zhongshan School of Medicine,Sun Yat-sen University,Guangzhou,China [8]Department of Immunology,Zhongshan School of Medicine,Sun Yat-sen University,Guangzhou,China [9]Guangzhou Center for Disease Control and Prevention,Guangzhou,China [10]Wuhan Metware Biotechnology Co.,Ltd,Wuhan,China [11]Department of Biomedical Sciences,New York Institute of Technology,College of Osteopathic Medicine,Old Westbury,NY,USA [12]Max Planck Institute for Heart and Lung Research and Cardiopulmonary Institute(CPI),Bad Nauheim,Germany [13]Department of Molecular Diagnostics,Sun Yat-sen Cancer Center,Sun Yat-sen University,Guangzhou,China [14]School of Public Health(Shenzhen),Sun Yat-sen University,Shenzhen,China [15]State Key Laboratory of Biocontrol,School of Life Sciences,Sun Yat-Sen University,Guangzhou,China [16]The Sixth Affiliated Hospital of Sun Yat-sen University,Guangzhou,China [17]Department of Endocrinology,Sun Yat-Sen Memorial Hospital,Sun Yat-sen University,Guangzhou,China [18]Guangzhou Regenerative Medicine and Health-Guangdong Laboratory(GRMH-GDL),Guangzhou Institutes of Biomedicine and Health,Chinese Academy of Sciences,Guangzhou,China [1

出　　处：《Signal Transduction and Targeted Therapy》2022年第1期270-281,共12页信号转导与靶向治疗（英文）

基　　金：This study was supported by the joint emergency grants for prevention and control of SARS-CoV-2 of Ministry of Science and Technology of China,Guangdong Science and Technology Department and Guangzhou Municipal Science and Technology Bureau(2020B111108001);Guangdong Science and Technology Department(2020B121206001&2020B1212030004);The funders had no role in study design,data collection and analysis,or preparation of the manuscript.

摘　　要：Abnormal glucose and lipid metabolism in COVID-19 patients were recently reported with unclear mechanism.In this study,we retrospectively investigated a cohort of COVID-19 patients without pre-existing metabolic-related diseases,and found new-onset in suli n resista nee,hyperglycemia,and decreased HDL-C in these patie nts.Mecha nistically,SARS-CoV-2 infecti on in creased the expression of RE1-silencing transcription factor(REST),which modulated the expression of secreted metabolic factors including myeloperoxidase,apelin,and myostatin at the transcriptional level,resulting in the perturbation of glucose and lipid metabolism.Furthermore,several lipids,including(±)5-HETE,(±)12-HETE,propionic acid,and isobutyric acid were identified as the potential biomarkers of COVID-19-induced metabolic dysregulation,especially in insulin resistance.Taken together,our study revealed insulin resistance as the direct cause of hyperglycemia upon COVID-19,and further illustrated the underlying mechanisms,providing potential therapeutic targets for COVID-19-induced metabolic complications.

关 键 词：metabolism mechanism resistance 

分 类 号：R563.1[医药卫生—呼吸系统] R589[医药卫生—内科学]