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

项目摘要/摘要 新冠肺炎已被证明是一种代谢性疾病，会导致不成比例的不良后果，令人痛苦 糖尿病或肥胖症患者。感染SARS-CoV-2并伴有高血糖的患者 住院时间、对机械通风的需求增加，与没有机械通风的人相比死亡率更高 高血糖症。我们发现，胰岛素抵抗而不是β细胞衰竭是导致 急性新冠肺炎中的高血糖。胰岛素增敏荷尔蒙脂联素在循环中减少 新冠肺炎患者与对照组之间的差异。此外，我们还证明了SARS-CoV-2可以直接感染 脂肪细胞。重要的是，我们在两个新冠肺炎尸检样本的脂肪组织中发现了复制病毒 患者和在小鼠和仓鼠实验模型中感染SARS-CoV-2。这些数据加在一起表明 SARS-CoV-2引发脂肪组织功能障碍导致胰岛素抵抗和不良结局 新冠肺炎。在这项建议中，我们寻求对这些研究进行后续研究，并评估导致肥胖的机制。 新冠肺炎急性期和恢复期模型的组织功能障碍。我们将追求以下具体目标：1. 评估急性SARS-CoV-2感染对肥胖和非肥胖小鼠血糖稳态的影响。2. 绘制SARS-CoV-2感染的空间分子相互作用图并剖析其分子机制 太胖了。3.确定SARS-CoV-2感染的长期糖代谢后果。总目标 其中一项研究是评估新冠肺炎如何导致脂肪组织功能障碍和高血糖，并将 阐明了对抗新冠肺炎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.