PERILIPINS AND CELLULAR TRIACYLGLYCEROL METABOLISM

周脂蛋白和细胞三酰甘油代谢

• 批准号: 6603562
• 负责人: DAWN L BRASAEMLE
• 金额: $ 24.48万
• 依托单位: RUTGERS, THE STATE UNIV OF N.J.
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-08-15 至 2005-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6603562
• 关键词: 3T3 cells; adipocytes; bioenergetics; carbohydrate metabolism; chimeric proteins; complementary DNA; cyclic AMP; cytoplasm; fluorescence microscopy; gene expression; glycerol; hydrolysis; immunofluorescence technique; intracellular transport; lipase; lipid metabolism; lipid transport; lipolysis; mutant; phosphoproteins; phosphorylation; protein kinase A; protein metabolism; protein structure function; triacylglycerol lipase

DESCRIPTION: (Adapted from the Investigator's Abstract): Obesity is a health problem that is reaching epidemic proportions in the United States and has become a major and growing factor contributing to an increased prevalence of Type II diabetes and an increased risk of premature death from cardiovascular disease. Despite the need for therapeutic options to control obesity, little is known about the intracellular mechanisms that regulate fat storage and release in adipose tissue. Fatty acids, the body's major energy currency, are stored as triacylglycerols in large intracellular lipid droplets in adipocytes. The perilipins are the most abundant proteins on the surfaces of lipid droplets in adipocytes and are also found in steroidogenic cells. The proposed studies test the hypotheses that 1) perilipins facilitate triacylglycerol storage by forming a protective barrier against cytosolic lipases, and 2) phosphorylation of perilipins facilitates lipolysis in lipolytically stimulated adipocytes by attenuating the barrier to facilitate lipase access to stored triacylglycerols. The Specific Aims of the proposed research are to 1) define the structural domains of perilipin A required for its targeting to and embedding into lipid droplets, 2) to study how perilipin A protects stored triacylglycerols from hormone-sensitive lipase, and 3) to elucidate the role of the phosphorylation of perilipin A in the promotion of lipolysis. These aims will be tested by the expression of intact and mutant perilipin A in cultured cells that lack perilipins followed by assays for lipid storage and release, and the presence of the mutant perilipins on lipid droplets.

描述：（改编自调查员的摘要）：肥胖是一种健康 在美国达到流行比例的问题 成为促使人们增加的主要因素 II型糖尿病和心血管过早死亡的风险增加 疾病。尽管需要治疗选择来控制肥胖，但很少 知道调节脂肪存储和释放的细胞内机制 在脂肪组织中。脂肪酸是人体的主要能源，被存储为 脂肪细胞中大细胞内脂质液滴中的三酰基甘油。这 围Perilipins是脂质液滴表面上最丰富的蛋白质 脂肪细胞，也存在于类固醇生成细胞中。提出的研究测试 假设1）围立替肽通过形成促进三酰基甘油的储存 针对胞质脂肪酶的保护屏障，2） Perilipins促进脂解的脂肪分解在脂肪刺激的脂肪细胞中通过 减轻障碍物，以促进脂肪酶进入储存的三酰基甘油。 拟议研究的具体目的是1）定义结构 Perilipin a的靶标需要其靶向并嵌入脂质中 液滴，2）研究perilipin a如何保护储存的三酰基甘油免受 激素敏感脂肪酶，3）阐明磷酸化的作用 促脂解促进脂解的peri蛋白A的含量。这些目标将由 在缺乏的培养细胞中表达完整和突变体围蛋白A 围血素，然后进行脂质储存和释放的测定，以及存在 脂质液滴上突变的围栏。