COVID-19 induces new-onset insulin resistance and lipid metabolic dysregulation via regulation of secreted metabolic factors
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, Zhong-wei Hu, Xilong Deng, Yueping Li, Xiaoneng Mo, Linghua Li, Yaling Shi, Yang Li, Yuan‐Yuan Zhu, Yanrong Wu, Huichao Liang, Baolin Liao, Wenxin Hong, Ruiying He, Jiao Jiao Li, Pengle Guo, Youguang Zhuo, Lingzhai Zhao, Fengyu Hu, Wenxue Li, Wei Zhu, Zefeng Zhang, Zeling Guo, Wei Zhang, Xiqiang Hong, Weikang Cai, Lei Gu, Ziming Du, Yang Zhang, Jin Xu, Tao Zuo, Kai Deng, Li Yan, Xinwen Chen, Sifan Chen, Chunliang Lei
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.