The Role of c-Cbl in Energy Homeostasis

c-Cbl 在能量稳态中的作用

• 批准号: 7394951
• 负责人: Kyle Lee hoehn
• 金额: $ 4.18万
• 依托单位: GARVAN INSTITUTE OF MEDICAL RESEARCH
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2009-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7394951
• 关键词: Ablation; Adipocytes; American; Animals; Body Weight; Ceramides; Condition; Data; Diabetes Mellitus; Energy Metabolism; Enzymes; Event; Fasting; Fatty acid glycerol esters; Glycogen (Starch) Synthase; Hibernation; Histocompatibility Testing; Homeostasis; Hyperphagia; Insulin; Insulin Resistance; Journals; Label; Link; MAP2K1 gene; MAPK8 gene; Mammals; Manuscripts; Marmota; Mediating; Metabolic; Metabolism; Mitochondria; Mitogen-Activated Protein Kinases; Molecular; Mus; Muscle; Obesity; Palmitates; Pathway interactions; Phenotype; Phosphorylation; Physiology; Polymerase Chain Reaction; Preparation; Process; Production; Protein Overexpression; Proteins; Publishing; RNA Interference; Regulation; Reporting; Role; Side; Specificity; Sphingolipids; Students; Therapeutic; Time; Tissues; Training; Tumor Necrosis Factor-alpha; cell type; enzyme activity; falls; fatty acid oxidation; human MAPK14 protein; human TNF protein; inhibitor/antagonist; mitogen-activated protein kinase p38; mixed lineage kinase 3; novel

Recent studies in this lab have identified c-Cbl as a key regulator of whole body energy expenditure and adiposity in mice. Ablation of c-Cbl in mice results in a desirable phenotype of reduced adiposity, increased lean body mass, small adipocytes, and increased energy expenditure despite hyperphagia. These mice illustrate a role for c-Cbl in an unknown facet of fuel metabolism that is integrally linked to body weight regulation. The majority of these metabolic changes occur in muscle and fat tissue, therefore the specific aims for this proposal are to 1) identify the tissue type that drives the c-Cbl -/- phenotype and 2) determine the molecular mechanism by which c-Cbl ablation results in increased fatty acid oxidation and reduced adiposity. Dissecting the c-Cbl -/- phenotype will illustrate the role of this protein in the molecular control of energy expenditure and have therapeutic applications in diabetes and obesity. The exciting aspect of these studies is that the molecular control of energy expenditure in mammals is a newly evolving field and the precise wiring diagram for this pathway has yet to be established. This study will identify novel inroads into this pathway and may pave the way for our understanding of mitochondrial energy expenditure.

该实验室最近的研究已经确定c-Cbl是全身能量消耗的关键调节因子， 小鼠肥胖症。小鼠中c-Cbl的消融导致期望的表型，即减少的肥胖、增加的肥胖、增加的肥胖、减少的肥胖、增加的肥胖 瘦体重、小脂肪细胞和尽管摄食过多但能量消耗增加。这些小鼠 说明c-Cbl在与体重整体相关燃料代谢的未知方面中的作用 调控这些代谢变化中的大多数发生在肌肉和脂肪组织中，因此， 该建议的目的是1）鉴定驱动c-Cbl -/-表型的组织类型，和2）确定 c-Cbl消融导致脂肪酸氧化增加和减少的分子机制 肥胖症剖析c-Cbl -/-表型将说明该蛋白在细胞凋亡的分子控制中的作用。 能量消耗，并且在糖尿病和肥胖症中具有治疗应用。这些令人兴奋的方面 研究表明，哺乳动物能量消耗的分子控制是一个新兴领域， 这一途径的精确线路图尚未确定。这项研究将确定新的入侵， 这一途径，并可能铺平道路，为我们了解线粒体能量消耗。