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
基本信息
- 批准号:10682138
- 负责人:
- 金额:$ 69万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 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:
- 关键词:2019-nCoVAcuteAdipocytesAdipose tissueAttenuatedAutomobile DrivingAutopsyBeta CellBiochemicalCOVID-19COVID-19 pandemicCOVID-19 patientCOVID-19 susceptibilityCell physiologyCellsCirculationCytometryDataDefectDiabetes MellitusDiseaseEndocrine GlandsExperimental ModelsFailureFatty acid glycerol estersFunctional disorderGenesGoalsHamstersHealthHomeostasisHormonesHyperglycemiaIRF3 geneImageImmunityImpairmentIndividualInfectionInflammatoryInsulinInsulin ResistanceInterferonsLength of StayLong COVIDMapsMechanical ventilationMetabolicMetabolic DiseasesModelingMolecularMorbidity - disease rateMusNon obeseNon-Insulin-Dependent Diabetes MellitusObese MiceObesityPathogenesisPathologyPathway interactionsPatientsPhysiologicalPlayRecoveryRoleSARS-CoV-2 infectionSARS-CoV-2 variantSamplingSpecimenTestingThinnessVirus ReplicationVulnerable Populationsadipokinesadiponectinadverse outcomeagedblood glucose regulationcell typecombatcomparison controlcoronavirus diseasefollow-upglucose metabolismglucose toleranceimpaired glucose tolerancein vivoinsulin secretioninsulin sensitivitymortalitymouse modelnovelnovel therapeuticspost SARS-CoV-2 infectionpreservationprogramspublic health relevancereceptorsymptom treatmenttrait
项目摘要
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
2019冠状病毒病。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血糖稳态的影响。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。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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James C Lo其他文献
Adipsin and Adipocyte-derived C3aR1 Regulate Thermogenic Fat in a Sex-dependent Fashion.
Adipsin 和脂肪细胞衍生的 C3aR1 以性别依赖性方式调节生热脂肪。
- DOI:
- 发表时间:
2024 - 期刊:
- 影响因子:8
- 作者:
Lunkun Ma;Ankit Gilani;Alfonso Rubio;Eric Cortada;Ang Li;Shannon M Reilly;Liling Tang;James C Lo - 通讯作者:
James C Lo
James C Lo的其他文献
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{{ truncateString('James C Lo', 18)}}的其他基金
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:
10835381 - 财政年份:2023
- 资助金额:
$ 69万 - 项目类别:
Alternative complement pathway regulation of beta cell homeostasis
β细胞稳态的替代补体途径调节
- 批准号:
10221291 - 财政年份:2020
- 资助金额:
$ 69万 - 项目类别:
Alternative complement pathway regulation of beta cell homeostasis
β细胞稳态的替代补体途径调节
- 批准号:
9886859 - 财政年份:2020
- 资助金额:
$ 69万 - 项目类别:
Alternative complement pathway regulation of beta cell homeostasis
β细胞稳态的替代补体途径调节
- 批准号:
10080727 - 财政年份:2020
- 资助金额:
$ 69万 - 项目类别:
Alternative complement pathway regulation of beta cell homeostasis
β细胞稳态的替代补体途径调节
- 批准号:
10530710 - 财政年份:2020
- 资助金额:
$ 69万 - 项目类别:
Alternative complement pathway regulation of beta cell homeostasis
β细胞稳态的替代补体途径调节
- 批准号:
10306383 - 财政年份:2020
- 资助金额:
$ 69万 - 项目类别:
An Obesity-Induced Kinase that Regulates Adipose Homeostasis and Metabolic Diseases
一种调节脂肪稳态和代谢疾病的肥胖诱导激酶
- 批准号:
10398840 - 财政年份:2019
- 资助金额:
$ 69万 - 项目类别:
An Obesity-Induced Kinase that Regulates Adipose Homeostasis and Metabolic Diseases
一种调节脂肪稳态和代谢疾病的肥胖诱导激酶
- 批准号:
10614524 - 财政年份:2019
- 资助金额:
$ 69万 - 项目类别:
Regulation of adipose inflammation and metabolic syndrome by adipsin/factor D
Adipsin/D 因子对脂肪炎症和代谢综合征的调节
- 批准号:
8425718 - 财政年份:2012
- 资助金额:
$ 69万 - 项目类别:
Regulation of adipose inflammation and metabolic syndrome by adipsin/factor D
Adipsin/D 因子对脂肪炎症和代谢综合征的调节
- 批准号:
8710209 - 财政年份:2012
- 资助金额:
$ 69万 - 项目类别:
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