Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, China.
Division of Vascular Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Signal Transduct Target Ther. 2021 Dec 16;6(1):427. doi: 10.1038/s41392-021-00822-x.
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.
新冠患者的糖脂代谢异常最近有报道，但具体机制尚不清楚。在这项研究中，我们回顾性调查了一组无预先存在代谢相关疾病的新冠患者，发现这些患者存在新发的胰岛素抵抗、高血糖和 HDL-C 降低。机制上，SARS-CoV-2 感染增加了 RE1 沉默转录因子（REST）的表达，REST 可在转录水平调节包括髓过氧化物酶、apelin 和肌肉生长抑制素在内的分泌代谢因子的表达，导致糖脂代谢紊乱。此外，几种脂质，包括（±）5-HETE、（±）12-HETE、丙酸和异丁酸被鉴定为 COVID-19 诱导代谢失调的潜在生物标志物，尤其是在胰岛素抵抗方面。总之，我们的研究揭示了胰岛素抵抗是新冠导致高血糖的直接原因，并进一步阐明了潜在的机制，为新冠引起的代谢并发症提供了潜在的治疗靶点。
