PERILIPINS AND CELLULAR TRIACYLGLYCEROL METABOLISM

周脂蛋白和细胞三酰甘油代谢

• 批准号: 6402590
• 负责人: DAWN L BRASAEMLE
• 金额: $ 23.72万
• 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 2004-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6402590
• 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：（改编自研究者摘要）：肥胖是一种健康 这个问题在美国已经达到了流行病的程度， 成为一个主要的和不断增长的因素，有助于增加流行的 II型糖尿病与心血管疾病过早死亡的风险增加 疾病尽管需要治疗选择来控制肥胖， 已知调节脂肪储存和释放的细胞内机制 在脂肪组织中。脂肪酸，身体的主要能量货币，储存为 脂肪细胞中大的细胞内脂滴中的三酰基甘油。的 脂周蛋白是在脂肪细胞中脂滴表面上最丰富的蛋白质， 脂肪细胞中，并且也在类固醇生成细胞中发现。拟议的研究测试 假设1）周脂蛋白通过形成 对胞质脂肪酶的保护屏障，和2）磷酸化 周脂蛋白通过以下途径促进脂解刺激的脂肪细胞中的脂解： 减弱屏障以促进脂肪酶接近储存的三酰基甘油。 本研究的具体目的是：1）确定结构 周脂蛋白A靶向和嵌入脂质所需的结构域 2）研究周脂蛋白A如何保护储存的三酰甘油， 酶敏感的脂肪酶，和3）阐明磷酸化的作用， perilipin A在促进脂肪分解中的作用。这些目标将由 完整和突变的周脂蛋白A在缺乏 周脂蛋白，然后测定脂质储存和释放， 突变的脂滴外脂蛋白。