THE ROLE OF OXPAT IN FAT TRAFFICKING AND SKELETAL MUSCLE METABOLISM

OXPAT 在脂肪运输和骨骼肌代谢中的作用

• 批准号: 8217238
• 负责人: NATHAN E WOLINS
• 金额: $ 33.06万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-02-01 至 2016-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8217238
• 关键词: 1,2-diacylglycerol; Ablation; Acyl Coenzyme A; Address; Adipocytes; Adipose tissue; Affect; Animals; Binding; Body Composition; Body Weight; Burn injury; Capsid Proteins; Cell Fractionation; Chimera organism; Cultured Cells; Cyclic AMP-Dependent Protein Kinases; Cytosol; Data; Diet; Diglycerides; Eating; Energy Metabolism; Enzymes; Exercise; Fasting; Fatty Acids; Fatty acid glycerol esters; Food; Food Energy; Glucose; Glycocalyx; Goals; Hormones; Hydrolysis; Hyperphagia; In Vitro; Lipase; Lipid Inclusion; Lipids; Lipolysis; Location; Mediating; Metabolic; Metabolic Diseases; Metabolism; Mitochondria; Mus; Muscle; Muscle Cells; Nutrient; Obesity; Organelles; Pathway interactions; Phosphorylation; Phosphorylation Site; Play; Predisposition; Proteins; Recruitment Activity; Regulation; Resistance; Role; Site; Skeletal Muscle; Testing; Training; Transgenic Mice; Triglycerides; adenylate kinase; diacylglycerol O-acyltransferase; fatty acid oxidation; feeding; genetic regulatory protein; in vivo; insulin sensitivity; lipid metabolism; muscle metabolism; overexpression; oxidation; perilipin; public health relevance; sterol esterase; synthetic enzyme; trafficking; transcription factor

DESCRIPTION (provided by applicant): The overall goal of these studies is to better understand factor that cause overeating-driven metabolic disease. We are using skeletal muscle, primary site of nutrient deposal, to address the role of protein that coat the myocellular fat depot (the perilipins) play in regulating the fat they enclose and how this regulation fat influences susceptibility to metabolic disease. We hypothesis: perilipin 5 forms the myocellular fat storage organelle; only fat in this organelle is under appropriate myocellular regulation; and perilipin 5 levels determine the fat storage capacity of organelle and the overflow this organelle cause metabolically disruptive lipid to leak in the cytosol. Thus, we predict that increasing perilipin 5 levels will increase resistant to metabolic challenges. We will determine: the effects of perilipins on cellular fat packaging and release; what lipid intermediates and key metabolic proteins perilipin 5 recruits fat droplets to regulate fat flux; and affect of muscle-specific overexpression and ablation of perilipin 5 on lipid metabolism, insulin sensitivity and levels of metabolically disruptive lipid. PUBLIC HEALTH RELEVANCE: We burn large amounts of food energy in our skeletal muscle, but eating more food than we burn leads to obesity. How fat is transported inside muscle cells and what regulates how fast fat is burned in muscle is not well understood. We propose to study the proteins in muscle cells that coat fat, and that transport fat into storage or direct fat to be burned as fuel.

描述（由申请人提供）：这些研究的总体目标是更好地理解导致暴饮暴食的代谢疾病的因素。我们正在使用骨骼肌，这是营养沉积的主要部位，以解决覆盖心肌脂肪仓库（围磷脂）在调节它们所包围的脂肪方面的作用，以及这种调节脂肪如何影响代谢疾病的易感性。我们的假设：Perilipin 5形成心肌脂肪储存细胞器；只有该细胞器中的脂肪才受到适当的心肌调节。 Perilipin 5水平决定了细胞器的脂肪储存能力和该细胞器的溢出会导致代谢上破坏性脂质在细胞质中泄漏。因此，我们预测，钙蛋白5水平的增加将增加对代谢挑战的抵抗力。我们将确定：围栏对细胞脂肪包装和释放的影响；哪些脂质中间体和关键代谢蛋白Peripin 5募集脂肪液滴来调节脂肪通量；以及肌肉特异性的过表达和perilipin 5对脂质代谢，胰岛素敏感性和代谢性破坏性脂质水平的影响。 公共卫生相关性：我们在骨骼肌中燃烧大量的食物能量，但是吃的食物比我们燃烧更多的食物会导致肥胖。脂肪在肌肉细胞内的运输方式以及调节肌肉中脂肪燃烧的速度的含量尚不清楚。我们建议研究涂层脂肪的肌肉细胞中的蛋白质，然后将脂肪输入储存或直接脂肪作为燃料燃烧。