PERILIPINS AND CELLULAR TRIACYLGLYCEROL METABOLISM

描述：(改编自《调查者摘要》)：肥胖是一种健康 这一问题在美国正达到流行病的程度，并已 成为一个主要且不断增长的因素，导致 II型糖尿病和心血管疾病过早死亡风险增加 疾病。尽管有必要选择治疗方法来控制肥胖，但几乎没有 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，人体的主要能源货币，被储存为 脂肪细胞内大的脂滴中的三酰甘油。这个 Perilipins是脂滴表面含量最丰富的蛋白质。 脂肪细胞，也存在于类固醇生成细胞中。建议的研究测试 假设1)糖脂促进三酰甘油的储存通过形成 针对胞浆脂肪酶的保护性屏障，以及2)磷酸化 Perilipins通过促进脂解刺激的脂肪细胞的脂解作用 减弱屏障以便于脂肪酶访问存储的三酰甘油。 拟议研究的具体目标是：1)定义结构 Perilipin A靶向和包埋脂质所需的结构域 液滴，2)研究Perilipin A如何保护储存的三酰甘油 激素敏感脂肪酶，以及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受到 完整和突变Perilipin A在缺失的培养细胞中的表达 Perilipins随后进行脂质储存和释放的分析，以及存在 突变的紫苏素在脂滴上的作用。

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.