Assessing the Impact of SARS-CoV-2 on Adipose Tissue Function and Glucose Homeostasis

项目总结/摘要 COVID-19已被证明是一种代谢性疾病，导致不良后果， 患有糖尿病或肥胖症的人。感染SARS-CoV-2和高血糖的患者遭受更长时间的 住院时间、机械通气需求和死亡率增加 高血糖症我们发现，胰岛素抵抗而不是β细胞衰竭是导致糖尿病的主要原因。 急性COVID-19高血糖症。胰岛素增敏激素脂联素在循环中减少 COVID-19患者与对照组相比。此外，我们证明SARS-CoV-2可以直接感染 脂肪细胞重要的是，我们在COVID-19尸检样本的脂肪组织中发现了复制病毒 患者以及SARS-CoV-2感染的小鼠和仓鼠实验模型。这些数据表明 SARS-CoV-2触发脂肪组织功能障碍，导致胰岛素抵抗和急性 新冠肺炎。在这项提案中，我们试图跟进这些研究，并评估驱动脂肪代谢的机制。 COVID-19急性和恢复模型中的组织功能障碍。我们将努力实现以下具体目标：1. 评估急性SARS-CoV-2感染对肥胖和非肥胖小鼠葡萄糖稳态的影响。2. 绘制空间分子相互作用图并剖析SARS-CoV-2感染的分子机制， 脂肪3.确定SARS-CoV-2感染的长期糖代谢后果。总目标 这些研究的目的是评估COVID-19如何导致脂肪组织功能障碍和高血糖症， 揭示了对抗COVID-19引起的代谢并发症的新靶点。

Project Summary/Abstract COVID-19 has proven to be a metabolic disease resulting in adverse outcomes disproportionally afflicting individuals with diabetes or obesity. Patients infected with SARS-CoV-2 and hyperglycemia suffer from longer hospital stays, increased need for mechanical ventilation and mortality compared to those without hyperglycemia. We found that insulin resistance rather than beta cell failure is the predominant cause of hyperglycemia in acute COVID-19. The insulin sensitizing hormone adiponectin is diminished in the circulation of COVID-19 patients compared to controls. Furthermore, we demonstrate that SARS-CoV-2 can directly infect adipocytes. Importantly, we find replicating virus in adipose tissues of both autopsy samples from COVID-19 patients and in mouse and hamster experimental models of SARS-CoV-2 infection. Together these data suggest that SARS-CoV-2 triggers adipose tissue dysfunction to drive insulin resistance and adverse outcomes in acute COVID-19. In this proposal, we seek to follow up on these studies and assess the mechanisms driving adipose tissue dysfunction in acute and recovered models of COVID-19. We will pursue the following specific aims: 1. Assess the impact of acute SARS-CoV-2 infection on glucose homeostasis in obese and non-obese mice. 2. Map the spatiomolecular interactions and dissect the molecular mechanisms of SARS-CoV-2 infection in adipose. 3. Determine the long-term glycometabolic consequences of SARS-CoV-2 infection. The overall goal of these studies is to assess how COVID-19 can drive adipose tissue dysfunction and hyperglycemia and will shed light on novel targets to combat metabolic complications induced by COVID-19.