The Role of c-Cbl in Energy Homeostasis

c-Cbl 在能量稳态中的作用

• 批准号: 7559322
• 负责人: Kyle Lee hoehn
• 金额: $ 0.79万
• 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/7559322
• 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.

本实验室最近的研究发现，c-Cbl是全身能量消耗的关键调节因子，并 小鼠的肥胖。C-Cbl在小鼠中的消融导致理想的表型：肥胖减少，肥胖增加 精瘦的身体质量，小的脂肪细胞，以及尽管吞噬过度仍增加的能量消耗。这些老鼠 说明c-Cbl在与体重密切相关的未知燃料代谢方面的作用 监管。这些代谢变化大多发生在肌肉和脂肪组织中，因此特定的 这项建议的目的是：1)确定驱动c-Cbl-/-表型的组织类型；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。对c-Cbl-/-表型的剖析将阐明该蛋白在人类免疫缺陷病毒的分子调控中的作用。 能量消耗，并在糖尿病和肥胖症方面有治疗应用。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的发展领域，而 这条通道的准确接线图尚未建立。这项研究将确定新的进入 这一途径可能为我们理解线粒体能量消耗铺平道路。