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; 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; Weikang Cai; Lei Gu; Ziming Du; Yang Zhang; Jin Xu; Tao Zuo; Kai Deng; Li Yan; Xinwen Chen; Sifan Chen; Chunliang Lei

doi:10.1038/s41392-021-00822-x

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, Zhongwei Hu, Xilong Deng, Yueping Li, Xiaoneng Mo, Linghua Li, Yaling ShiLi 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, Weikang Cai, Lei Gu, Ziming Du, Yang Zhang, Jin Xu, Tao Zuo, Kai Deng, Li Yan, Xinwen Chen, Sifan Chen, Chunliang Lei

Research output: Contribution to journal › Article › peer-review

81 Scopus citations

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.

Original language	English
Article number	427
Journal	Signal Transduction and Targeted Therapy
Volume	6
Issue number	1
DOIs	https://doi.org/10.1038/s41392-021-00822-x
State	Published - Dec 2021

Bibliographical note

Publisher Copyright:
© 2021, The Author(s).

Funding

We thank Prof. Hui Zhang lab (Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University) for providing the SARS-CoV-2 virus strain. 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), and Guangdong Science and Technology Department (2020B1212060018, 2020B1212030004). The funders had no role in study design, data collection and analysis, or preparation of the manuscript.

Funders	Funder number
Guangdong Science and Technology Department and Guangzhou Municipal Science and Technology Bureau
Ministry of Science and Technology of the People's Republic of China
Guangdong Science and Technology Department	2020B111108001, 2020B1212030004, 2020B1212060018
Guangdong Science and Technology Department

ASJC Scopus subject areas

Genetics
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s41392-021-00822-x

Cite this

He, X., Liu, C., Peng, J., Li, Z., Li, F., Wang, J., Hu, A., Peng, M., Huang, K., Fan, D., Li, N., Zhang, F., Cai, W., Tan, X., Hu, Z., Deng, X., Li, Y., Mo, X., Li, L., ... Lei, C. (2021). COVID-19 induces new-onset insulin resistance and lipid metabolic dysregulation via regulation of secreted metabolic factors. Signal Transduction and Targeted Therapy, 6(1), Article 427. https://doi.org/10.1038/s41392-021-00822-x

@article{819e342772de4aa8844e599f618d7433,

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

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.",

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

note = "Publisher Copyright: {\textcopyright} 2021, The Author(s).",

year = "2021",

month = dec,

doi = "10.1038/s41392-021-00822-x",

language = "English",

volume = "6",

number = "1",

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He, X, Liu, C, Peng, J, Li, Z, Li, F, Wang, J, Hu, A, Peng, M, Huang, K, Fan, D, Li, N, Zhang, F, Cai, W, Tan, X, Hu, Z, Deng, X, Li, Y, Mo, X, Li, L, Shi, Y, Yang, L, Zhu, Y, Wu, Y, Liang, H, Liao, B, Hong, W, He, R, Li, J, Guo, P, Zhuo, Y, Zhao, L, Hu, F, Li, W, Zhu, W, Zhang, Z, Guo, Z, Zhang, W, Hong, X, Cai, W, Gu, L, Du, Z, Zhang, Y, Xu, J, Zuo, T, Deng, K, Yan, L, Chen, X, Chen, S & Lei, C 2021, 'COVID-19 induces new-onset insulin resistance and lipid metabolic dysregulation via regulation of secreted metabolic factors', Signal Transduction and Targeted Therapy, vol. 6, no. 1, 427. https://doi.org/10.1038/s41392-021-00822-x

TY - JOUR

T1 - COVID-19 induces new-onset insulin resistance and lipid metabolic dysregulation via regulation of secreted metabolic factors

AU - He, Xi

AU - Liu, Chenshu

AU - Peng, Jiangyun

AU - Li, Zilun

AU - Li, Fang

AU - Wang, Jian

AU - Hu, Ao

AU - Peng, Meixiu

AU - Huang, Kan

AU - Fan, Dongxiao

AU - Li, Na

AU - Zhang, Fuchun

AU - Cai, Weiping

AU - Tan, Xinghua

AU - Hu, Zhongwei

AU - Deng, Xilong

AU - Li, Yueping

AU - Mo, Xiaoneng

AU - Li, Linghua

AU - Shi, Yaling

AU - Yang, Li

AU - Zhu, Yuanyuan

AU - Wu, Yanrong

AU - Liang, Huichao

AU - Liao, Baolin

AU - Hong, Wenxin

AU - He, Ruiying

AU - Li, Jiaojiao

AU - Guo, Pengle

AU - Zhuo, Youguang

AU - Zhao, Lingzhai

AU - Hu, Fengyu

AU - Li, Wenxue

AU - Zhu, Wei

AU - Zhang, Zefeng

AU - Guo, Zeling

AU - Zhang, Wei

AU - Hong, Xiqiang

AU - Cai, Weikang

AU - Gu, Lei

AU - Du, Ziming

AU - Zhang, Yang

AU - Xu, Jin

AU - Zuo, Tao

AU - Deng, Kai

AU - Yan, Li

AU - Chen, Xinwen

AU - Chen, Sifan

AU - Lei, Chunliang

PY - 2021/12

Y1 - 2021/12

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85121446388

UR - https://www.scopus.com/inward/citedby.url?scp=85121446388&partnerID=8YFLogxK

U2 - 10.1038/s41392-021-00822-x

DO - 10.1038/s41392-021-00822-x

M3 - Article

C2 - 34916489

AN - SCOPUS:85121446388

SN - 2095-9907

VL - 6

JO - Signal Transduction and Targeted Therapy

JF - Signal Transduction and Targeted Therapy

IS - 1

M1 - 427

ER -

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

Abstract

Bibliographical note

Funding

ASJC Scopus subject areas

UN SDGs

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