COVID-19 induces new-onset insulin resistance and lipid metabolic dysregulation via regulation of secreted metabolic factors.
COVID-19 induces new-onset insulin resistance and lipid metabolic dysregulation via regulation of secreted metabolic factors.
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DOI：
10.1038/s41392-021-00822-x
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发表时间：
2021-12-16
影响因子：
39.3
通讯作者：
Lei C
中科院分区：
文献类型：
--
作者：
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
近年来有报道称COVID-19患者出现糖脂代谢异常，但其机制尚不清楚。在这项研究中，我们回顾性调查了一组既往无代谢相关疾病的COVID-19患者，并在这些患者中发现了新发胰岛素抵抗、高血糖和HDL-C降低。从机制上讲，SARS-CoV-2感染增加了RE 1沉默转录因子（REST）的表达，REST在转录水平上调节了分泌的代谢因子（包括髓过氧化物酶、爱帕琳蛋白和肌肉生长抑制素）的表达，导致葡萄糖和脂质代谢紊乱。此外，包括（±）5-HETE、（±）12-HETE、丙酸和异丁酸在内的几种脂质被确定为COVID-19诱导的代谢失调的潜在生物标志物，尤其是在胰岛素抵抗中。综上所述，我们的研究揭示了胰岛素抵抗是COVID-19高血糖症的直接原因，并进一步阐明了潜在的机制，为COVID-19诱导的代谢并发症提供了潜在的治疗靶点。
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.
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影响因子：
29
作者：
Coate KC;Cha J;Shrestha S;Wang W;Gonçalves LM;Almaça J;Kapp ME;Fasolino M;Morgan A;Dai C;Saunders DC;Bottino R;Aramandla R;Jenkins R;Stein R;Kaestner KH;Vahedi G;HPAP Consortium;Brissova M;Powers AC
通讯作者：
Powers AC
影响因子：
39.3
作者：
Li Y;Hou G;Zhou H;Wang Y;Tun HM;Zhu A;Zhao J;Xiao F;Lin S;Liu D;Zhou D;Mai L;Zhang L;Zhang Z;Kuang L;Guan J;Chen Q;Wen L;Zhang Y;Zhuo J;Li F;Zhuang Z;Chen Z;Luo L;Liu D;Chen C;Gan M;Zhong N;Zhao J;Ren Y;Xu Y
通讯作者：
Xu Y
影响因子：
4.6
作者：
Masana L;Correig E;Ibarretxe D;Anoro E;Arroyo JA;Jericó C;Guerrero C;Miret M;Näf S;Pardo A;Perea V;Pérez-Bernalte R;Plana N;Ramírez-Montesinos R;Royuela M;Soler C;Urquizu-Padilla M;Zamora A;Pedro-Botet J;STACOV-XULA research group
通讯作者：
STACOV-XULA research group
影响因子：
20.8
作者：
Montefusco, Laura;Ben Nasr, Moufida;D'Addio, Francesca;Loretelli, Cristian;Rossi, Antonio;Pastore, Ida;Daniele, Giuseppe;Abdelsalam, Ahmed;Maestroni, Anna;Dell'Acqua, Marco;Ippolito, Elio;Assi, Emma;Usuelli, Vera;Seelam, Andy Joe;Fiorina, Roberta Maria;Chebat, Enrica;Morpurgo, Paola;Lunati, Maria Elena;Bolla, Andrea Mario;Finzi, Giovanna;Abdi, Reza;Bonventre, Joseph V.;Rusconi, Stefano;Riva, Agostino;Corradi, Domenico;Santus, Pierachille;Nebuloni, Manuela;Folli, Franco;Zuccotti, Gian Vincenzo;Galli, Massimo;Fiorina, Paolo
通讯作者：
Fiorina, Paolo
影响因子：
64.5
作者：
CHONG, JHA;TAPIARAMIREZ, J;MANDEL, G
通讯作者：
MANDEL, G