Perilipins and cellular triacyglycerol metabolism

Perilipins 和细胞三酰甘油代谢

基本信息

批准号：
7996466
负责人：
DAWN L BRASAEMLE
金额：
$ 1.91万
依托单位：
RUTGERS, THE STATE UNIV OF N.J.
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-03-01 至 2011-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7996466
关键词：
1,2-diacylglycerol Abbreviations Address Adipocytes Adipose tissue Affect Alanine Amino Acid Sequence Amino Acids Aspartic Acid Binding Biological Assay Cardiovascular Diseases Cells Chimera organism Chimeric Proteins Chinese Hamster Cholesterol Esters Cultured Cells Cyclic AMP-Dependent Protein Kinases Diglycerides Disease Docking Drops Ectopic Hormones Energy Metabolism Energy-Generating Resources Enzymes Fatty Acids Fatty acid glycerol esters Fibroblasts Forskolin Glutamic Acid Goals Green Fluorescent Proteins Health Hormonal Human Hydrolase Immunoblotting Immunofluorescence Microscopy In Vitro Incubated Insecta Isoproterenol Lipase Lipids Lipolysis Malignant Neoplasms Mass Spectrum Analysis Mediating Metabolic Metabolism Molecular Monoglycerides Mutate Mutation Non-Insulin-Dependent Diabetes Mellitus Nucleotides Obesity Organelles Ovary Patients Phospholipid Metabolism Phosphorylation Play Point Mutation Prevalence Proteins Proteomics RNA Interference Recombinant Proteins Recombinants Regulation Research Research Personnel Role Serine Site Site-Directed Mutagenesis Surface Testing Therapeutic Tissues Transferase Triglycerides adipophilin caveolin 1 fatty acid-binding proteins feeding insulin sensitivity member perilipin perilipin A programs protein protein interaction research study scaffold sterol esterase umbelliferyl phosphate

项目摘要

DESCRIPTION (provided by applicant): Obesity is a serious health problem throughout the world, and contributes to an increased prevalence of Type II diabetes, cardiovascular disease, and cancer. Despite a need for therapeutic options to treat obesity, little is known about the mechanisms that regulate fat storage and release from adipocytes. Triacylglycerols (TAG), the body's major storage form of energy, are packaged in lipid droplets in adipocytes that are covered with perilipin A, a protein that plays a critical role in controlling TAG storage and lipolysis to release fatty acids that serve as a major source of energy. The proposed studies will elucidate the molecular mechanisms by which perilipin A coordinates adipocyte TAG metabolism. Preliminary studies have provided evidence that hormone-sensitive lipase (HSL), and CGI-58, a protein important for TAG metabolism, associate with lipid droplets via a mechanism that is responsive to the phosphorylation state of perilipin A. The proposed studies will test the hypotheses that 1) the phosphorylation of perilipin A controls lipolysis through multiple complementary mechanisms, and 2) that perilipin A serves as an organizing center that coordinates the association of TAG catabolic enzymes with lipid droplets in a manner that is responsive to the lipolytic status of the adipocyte. Specifically, we will 1) elucidate the mechanisms by which perilipin A facilitates the docking of HSL on lipid droplets, 2) identify additional mechanisms by which phosphorylated perilipin A coordinates lipolysis that are distinct from its role in facilitating HSL docking, and 3) elucidate the role that perilipin A plays in docking CGI-58 on lipid droplets and the consequences of this functional interaction to TAG metabolism. Intact and mutated perilipins and HSL or CGI-58 will be expressed in cultured cells that lack these proteins followed by assays for TAG storage and lipolysis; additionally, RNAi approaches and in vitro studies of recombinant proteins are proposed. These studies will contribute to a long-term goal of defining the factors on lipid droplets that control adipocyte TAG metabolism.

描述（由申请人提供）：肥胖是全球一个严重的健康问题，并导致II型糖尿病，心血管疾病和癌症的患病率增加。尽管需要治疗肥胖症的治疗选择，但对调节脂肪储存和脂肪细胞释放的机制知之甚少。人体的主要能量储存形式（TAG）包装在脂肪细胞中的脂质液滴中，这些脂肪细胞上覆盖着紫脂蛋白A（一种蛋白质），该蛋白质在控制标签储存和脂解中起着至关重要的作用，以释放脂肪酸，这些脂肪酸是主要能量来源的脂肪酸。拟议的研究将阐明紫脂蛋白A协调脂肪细胞TAG代谢的分子机制。初步研究提供了证据表明，激素敏感的脂肪酶（HSL）和CGI-58（一种对TAG代谢很重要的蛋白质）通过一种机制与脂质液滴相关的机制，该机制响应着Perilipin的磷酸化状态A.拟议的研究将通过perlostiply Androplysiraligals perlostiply Androptipil andiply andiplations ronplostipiles sytiplations controptipin。 Perilipin A充当组织中心，以对脂肪细胞的脂解状态有反应的方式将TAG分解代谢酶与脂质液滴的关联进行协调。 Specifically, we will 1) elucidate the mechanisms by which perilipin A facilitates the docking of HSL on lipid droplets, 2) identify additional mechanisms by which phosphorylated perilipin A coordinates lipolysis that are distinct from its role in facilitating HSL docking, and 3) elucidate the role that perilipin A plays in docking CGI-58 on lipid droplets以及这种功能相互作用对标记代谢的后果。完整和突变的围蛋白以及HSL或CGI-58将在缺乏这些蛋白质的培养细胞中表达，然后进行标记储存和脂肪分解的测定。另外，提出了RNAi方法和重组蛋白的体外研究。这些研究将有助于定义控制脂肪细胞TAG代谢的脂质液滴的因素。