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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.

SUBMITTER: He X 

PROVIDER: S-EPMC8674414 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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

He Xi X   Liu Chenshu C   Peng Jiangyun J   Li Zilun Z   Li Fang F   Wang Jian J   Hu Ao A   Peng Meixiu M   Huang Kan K   Fan Dongxiao D   Li Na N   Zhang Fuchun F   Cai Weiping W   Tan Xinghua X   Hu Zhongwei Z   Deng Xilong X   Li Yueping Y   Mo Xiaoneng X   Li Linghua L   Shi Yaling Y   Yang Li L   Zhu Yuanyuan Y   Wu Yanrong Y   Liang Huichao H   Liao Baolin B   Hong Wenxin W   He Ruiying R   Li Jiaojiao J   Guo Pengle P   Zhuo Youguang Y   Zhao Lingzhai L   Hu Fengyu F   Li Wenxue W   Zhu Wei W   Zhang Zefeng Z   Guo Zeling Z   Zhang Wei W   Hong Xiqiang X   Cai Weikang W   Gu Lei L   Du Ziming Z   Zhang Yang Y   Xu Jin J   Zuo Tao T   Deng Kai K   Yan Li L   Chen Xinwen X   Chen Sifan S   Lei Chunliang C  

Signal transduction and targeted therapy 20211216 1


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 incl  ...[more]

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