Targeting the hepatic adropin signaling pathway in obesity
靶向肥胖中的肝脏 adropin 信号通路
基本信息
- 批准号:10677279
- 负责人:
- 金额:$ 4.32万
- 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:2023-04-01 至 2024-01-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAnimal ModelApoptosisAtherosclerosisBiochemicalBioenergeticsBiological ProcessBrainCardiacCell membraneCellsComplexCoronary ArteriosclerosisDefectDevelopmentDiabetes MellitusDietDiseaseDisease ProgressionEducationEndotheliumEnergy Metabolism PathwayEnzymesEssential GenesExhibitsFatty AcidsFatty LiverFatty acid glycerol estersFellowshipFibrosisG-Protein-Coupled ReceptorsGenetic DiseasesGlucoseGoalsHeartHepaticHepatocyteHistologicHomeostasisImmunohistochemistryImpairmentIn VitroInflammationInflammatory ResponseKnock-outKnockout MiceLigandsLinkLipidsLiverMeasuresMediatingMediatorMetabolicMetabolic DiseasesMetabolismMolecularNull LymphocytesNutrientNutrition DisordersObesityObesity associated diseaseObesity associated liver diseaseOrphanPPAR gammaPathologicPathologyPeripheralPhenotypePopulationPrevalenceRecombinantsRegulationRegulatory PathwayResearchResistanceRisk FactorsRoleSignal PathwaySignal TransductionTechniquesTestingTherapeutic EffectTissuesTrainingUnited StatesUp-RegulationWestern BlottingWild Type Mouseblood glucose regulationcareerdesigndiabeticeffective therapyhuman subjectin vivolipid metabolismliver developmentliver injurymouse modelnon-alcoholic fatty liver diseasenonalcoholic steatohepatitisnoveloxidationoxidative damagepeptide hormonepreventable deathprotective effectreceptorresponseuptake
项目摘要
PROJECT SUMMARY/ABSTRACT
Obesity is the second leading cause of preventable death in the United States. Obesity is a complex nutritional
and genetic disorder that is driven by energy imbalances, and serves as a fundamental risk factor in various
pathologies including coronary artery disease, diabetes, non-alcoholic fatty liver disease, and atherosclerosis.
The cellular and molecular mechanisms that drive obesity-related disease in different tissues are not fully
elucidated, and this represents an impediment to the development of effective and efficient treatments. Adropin
is a recently characterized liver- and brain-derived peptide hormone that exerts powerful effects on fuel
substrate metabolism in peripheral tissues. Adropin levels are significantly reduced in obese and diabetic
human subjects, and this decrease is linked to increased adiposity and impaired glucose homeostasis.
Furthermore, adropin depletion has been linked with the development of liver-associated obesity diseases
such as NAFLD and NASH. In this fellowship application, we will determine the molecular signaling pathways
underlying adropin function in liver fuel metabolism, and investigate its protective effects against NAFLD and
NASH. In Aim 1, we will determine how adropin associates with the cell membrane receptor GPR19 to regulate
hepatocyte fuel metabolism. In Aim 2, we will determine if GPR19 is necessary for the protective effects of
adropin against hepatic injury. By combining cutting-edge metabolic techniques and a comprehensive training
plan, this fellowship will allow me to prepare for the next stage of my career in metabolic research and scientific
education.
项目总结/摘要
肥胖是美国可预防死亡的第二大原因。肥胖是一种复杂的营养
和遗传性疾病,这是由能量不平衡驱动,并作为一个基本的风险因素,在各种
病理学包括冠状动脉疾病、糖尿病、非酒精性脂肪肝疾病和动脉粥样硬化。
在不同组织中驱动肥胖相关疾病的细胞和分子机制并不完全
阐明,这代表了发展有效和高效治疗的障碍。阿德罗平
是一种最近鉴定的肝脏和大脑来源的肽激素,对燃料产生强大的影响。
外周组织中的底物代谢。在肥胖和糖尿病患者中,
人类受试者,这种减少与肥胖增加和葡萄糖稳态受损有关。
此外,肾上腺素耗竭与肝脏相关性肥胖疾病的发展有关
如NAFLD和NASH。在这个奖学金申请中,我们将确定分子信号通路
Adropin在肝脏燃料代谢中的潜在功能,并研究其对NAFLD的保护作用,
纳什在目的1中,我们将确定Adropin如何与细胞膜受体GPR 19结合,以调节细胞内的细胞凋亡。
肝细胞燃料代谢。在目标2中,我们将确定GPR 19是否是保护作用所必需的。
Adropin抗肝损伤。通过结合尖端的新陈代谢技术和全面的训练
计划,这个奖学金将使我为我的代谢研究和科学事业的下一阶段做好准备。
教育
项目成果
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