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

Xiaoyun He ,Jian Wang,Fuchun Zhang,Ruiying He,Xiaoneng Mo,Youguang Zhuo,Li Yang,Linghua Li,Xiqiang Hong,Fang Li,Weikang Cai,Wei Cai ,Wenxue Li,Ling Gu ,Xilong Deng,Mingying Peng ,Yuan‐Yuan Zhu ,Anbin Hu ,Jin Xu,Kan Huang,Zefeng Zhang,Kai Deng,Dongxiao Fan,Na Li,Tao Zuo,Yanrong Wu,Sifan Chen,Yang Zhou ,Xinghua Tan,Chenshu Liu,Wei Hong ,Yawei Shi ,Pengle Guo,Baolin Liao,Xinwen Chen,Zilun Li,Li Yan,Fengyu Hu,Liang Zhao ,Wei Zhu,Wei Zhang,Jiaojiao Li,Zhiqiang Guo ,Zhongwei Huang ,Ziwei Du ,Yueping Liu ,Jiangyun Peng,Huihong Liang ,Chunliang Lei

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.

Highlights

Coronavirus disease 2019 (COVID-19) has spread worldwide and resulted in 251,266,207 confirmed cases, with the death toll rising to 5,070,244 as to November 10, 2021
19 patients, which might potentially shed light on the patients, the clinical data of patients diagnosed with COVID-19 illustration of mechanism regarding COVID-19-associated between January 22, 2020 and April 7, 2020 in Guangzhou Eighth metabolic dysregulation
Considering that MPO, apelin, and myostatin showed consistent alteration patterns upon COVID-19, which is in line with their previously identified regulatory roles, we explored the potential association between MPO, apelin, and myostatin and metabolic parameters

Summary

INTRODUCTION

Coronavirus disease 2019 (COVID-19) has spread worldwide and resulted in 251,266,207 confirmed cases, with the death toll rising to 5,070,244 as to November 10, 2021 (https://covid19.who.int/). Our study reported insulin resistance, instead of insulin deficiency, as COVID-19 in comparison with COVID-19-negative ARDS patients was reported.[19] These studies suggested another potential hypothesis that COVID-19 may cause insulin resistance, resulting the main pathophysiology behind the hyperglycemia observed in COVID-19 patients, and further illustrated the underlying mechanism, which will be of great significance in clinical treatment and in hyperglycemia. It is still highly debatable whether follow-up study for metabolic complications of COVID-19 patients. It is still highly debatable whether follow-up study for metabolic complications of COVID-19 patients. insulin deficiency or insulin resistance drives the progress of hyperglycemia in COVID-19, and more clinical data and mechanistic studies are required

RESULTS

Limitations of the study

MATERIALS AND METHODS

Study design and participants