Analysis of Lipolytic Trafficking in Muscle

肌肉中脂肪分解运输的分析

• 批准号: 8762419
• 负责人: James G Granneman
• 金额: --
• 依托单位: JOHN D DINGELL VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-10-01 至 2015-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8762419
• 关键词: Adipocytes; Adipose tissue; Affect; Binding; Biological; Biological Assay; Brown Fat; Buffers; Cardiovascular Diseases; Cell Respiration; Cell physiology; Cells; Diabetes Mellitus; Disease; Electrons; Elements; Equilibrium; Fasting; Fatty Acids; Fatty acid glycerol esters; Genes; Goals; Grant; Health; Heart; Hormones; Human; Hydrolase; In Vitro; Insulin; Insulin Resistance; Intracellular Accumulation of Lipids; Knowledge; Life; Lipase; Lipid Mobilization; Lipids; Lipolysis; Liver; Mammals; Mediating; Metabolic; Microscopic; Mitochondria; Modeling; Molecular; Muscle; Muscle Cells; Nonesterified Fatty Acids; Obesity; Peripheral; Phosphoproteins; Phosphorylation; Play; Process; Proteins; Proteomics; Relative (related person); Resolution; Role; Site; Source; Surface; Techniques; Testing; Therapeutic Intervention; Tissues; Triglycerides; Work; cellular imaging; feeding; flexibility; in vivo; loss of function; novel; obesity treatment; oxidation; perilipin; protein protein interaction; small molecule; theories; trafficking; transmission process

DESCRIPTION (provided by applicant): The storage and mobilization of lipids are fundamental cellular processes. In mammals, adipose tissue functions as a specialized lipid buffer that stores excess energy as triglyceride for systemic mobilization as free fatty acids (FFA). Nonetheless, virtually all cells have the ability to store and mobilize FFA; indeed, for some tissues FFA can provide the major source of metabolic energy. Excessive FFA can disrupt cellular function in a process that has been termed 'lipotoxicity," which is thought to be a major means by which obesity contributes to diabetes and cardiovascular disease. In theory, lipotoxicity can be brought about by excessive systemic supply of FFA from adipose tissue, or by an imbalance in FFA storage and mobilization in peripheral tissues. Thus, a mechanistic understanding of how cells assimilate, mobilize and channel FFA is an important biological question with broad implications for health and disease. Our long term goal is to provide a mechanistic understanding of cellular lipolysis so as to identify novel points of therapeutic intervention for the treatment of obesity and diabetes. We hypothesize that intracellular lipolysis in muscle is controlled by the orderly trafficking of specific proteins at the surface of specialized lipid droplets. This work will define the intracellular sites where lipolysis occurs, test specific models of dynamic protein- protein interactions, and determine the functional impact of those interactions in vitro and in vivo.

描述（由申请人提供）： 脂质的存储和动员是基本的细胞过程。在哺乳动物中，脂肪组织充当一种专门的脂质缓冲液，将多余的能量作为甘油三酸酯作为全身动员作为游离脂肪酸（FFA）。但是，几乎所有细胞都具有存储和动员FFA的能力。确实，对于某些组织而言，FFA可以提供代谢能的主要来源。过度的FFA会在被称为“脂蛋白毒性”的过程中破坏细胞功能，这被认为是肥胖有助于糖尿病和心血管疾病的主要手段。从理论上讲，脂蛋白毒性可以通过过度的脂肪毒性来引起脂肪毒性，从而使FFA在脂肪组织中或在脂肪组织中供应量不大，或者在脂肪组织中供应，或者是通过脂肪组织中的AI含量的机制而在FFA中掌握的，而动物的机器化则可以在FFA中掌握。同化，动员和渠道FFA是一个重要的生物学问题，我们的长期目标是对细胞脂解的机械理解，以确定治疗肥胖和糖尿病的治疗方法工作将定义发生脂解的细胞内部位，测试动态蛋白质相互作用的特定模型，并确定这些相互作用在体外和体内的功能影响。