2. Academic Validation
  3. COVID-19 induces new-onset insulin resistance and lipid metabolic dysregulation via regulation of secreted metabolic factors

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

  • Signal Transduct Target Ther. 2021 Dec 16;6(1):427. doi: 10.1038/s41392-021-00822-x.
Xi He  # 1,  Chenshu Liu  # 2 3,  Jiangyun Peng  # 4 5,  Zilun Li  # 2 3,  Fang Li  # 1 6,  Jian Wang 1,  Ao Hu 7 8,  Meixiu Peng 3,  Kan Huang 2 3,  Dongxiao Fan 2 3,  Na Li 2 3,  Fuchun Zhang 1,  Weiping Cai 1,  Xinghua Tan 1,  Zhongwei Hu 1,  Xilong Deng 1,  Yueping Li 1,  Xiaoneng Mo 1,  Linghua Li 1,  Yaling Shi 1,  Li Yang 1,  Yuanyuan Zhu 1,  Yanrong Wu 1,  Huichao Liang 1,  Baolin Liao 1,  Wenxin Hong 1,  Ruiying He 1,  Jiaojiao Li 1,  Pengle Guo 1,  Youguang Zhuo 1,  Lingzhai Zhao 1,  Fengyu Hu 1,  Wenxue Li 9,  Wei Zhu 9,  Zefeng Zhang 4 5,  Zeling Guo 3,  Wei Zhang 10,  Xiqiang Hong 10,  Weikang Cai 11,  Lei Gu 12,  Ziming Du 13,  Yang Zhang 14,  Jin Xu 15,  Tao Zuo 16,  Kai Deng 7 8,  Li Yan 17,  Xinwen Chen 18 19,  Sifan Chen 20 21,  Chunliang Lei 22
Affiliations

Affiliations

  • 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. chen_xinwen@gibh.ac.cn.
  • 19 Key Laboratory of Regenerative Biology of the Chinese Academy of Sciences and Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China. chen_xinwen@gibh.ac.cn.
  • 20 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. chensf26@mail.sysu.edu.cn.
  • 21 Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China. chensf26@mail.sysu.edu.cn.
  • 22 Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, China. gz8hlcl@126.com.
  • # Contributed equally.
PMID: 34916489 DOI: 10.1038/s41392-021-00822-x
Abstract

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 Insulin resistance, hyperglycemia, and decreased HDL-C in these patients. Mechanistically, SARS-CoV-2 Infection increased 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.

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