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

评估 SARS-CoV-2 对脂肪组织功能和血糖稳态的影响

• 批准号: 10682138
• 负责人: James C Lo
• 金额: $ 69万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-01 至 2028-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10682138
• 关键词: 2019-nCoV; Acute; Adipocytes; Adipose tissue; Attenuated; Automobile Driving; Autopsy; Beta Cell; Biochemical; COVID-19; COVID-19 pandemic; COVID-19 patient; COVID-19 susceptibility; Cell physiology; Cells; Circulation; Cytometry; Data; Defect; Diabetes Mellitus; Disease; Endocrine Glands; Experimental Models; Failure; Fatty acid glycerol esters; Functional disorder; Genes; Goals; Hamsters; Health; Homeostasis; Hormones; Hyperglycemia; IRF3 gene; Image; Immunity; Impairment; Individual; Infection; Inflammatory; Insulin; Insulin Resistance; Interferons; Length of Stay; Long COVID; Maps; Mechanical ventilation; Metabolic; Metabolic Diseases; Modeling; Molecular; Morbidity - disease rate; Mus; Non obese; Non-Insulin-Dependent Diabetes Mellitus; Obese Mice; Obesity; Pathogenesis; Pathology; Pathway interactions; Patients; Physiological; Play; Recovery; Role; SARS-CoV-2 infection; SARS-CoV-2 variant; Sampling; Specimen; Testing; Thinness; Virus Replication; Vulnerable Populations; adipokines; adiponectin; adverse outcome; aged; blood glucose regulation; cell type; combat; comparison control; coronavirus disease; follow-up; glucose metabolism; glucose tolerance; impaired glucose tolerance; in vivo; insulin secretion; insulin sensitivity; mortality; mouse model; novel; novel therapeutics; post SARS-CoV-2 infection; preservation; programs; public health relevance; receptor; symptom treatment; trait

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.

项目摘要/摘要 Covid-19已被证明是一种代谢疾病，导致不利的结果不成比例 患有糖尿病或肥胖症的人。感染SARS-COV-2和高血糖的患者患有更长的患者 与没有 高血糖。我们发现胰岛素抵抗而不是β细胞衰竭是 急性共卷19中的高血糖。胰岛素敏感激素脂联素在循环中减少 与对照组相比，199名患者的共同患者。此外，我们证明SARS-COV-2可以直接感染 脂肪细胞。重要的是，我们在两种尸检样品的脂肪组织中发现复制病毒。 患者以及SARS-COV-2感染的小鼠和仓鼠实验模型。这些数据一起暗示 SARS-COV-2触发脂肪组织功能障碍以驱动胰岛素抵抗和急性不良结果 新冠肺炎。在此提案中，我们试图跟进这些研究并评估驱动脂肪的机制 急性和回收模型19的组织功能障碍。我们将追求以下特定目标：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。 绘制空格分子相互作用并剖析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。总体目标 这些研究是评估Covid-19如何驱动脂肪组织功能障碍和高血糖症，并将 阐明了新型靶标，以应对COVID-19引起的代谢并发症。