ENDOGENOUS LIGANDS FOR PPAR-GAMMA

核激素受体，过氧化物酶体增殖物激活受体 伽马(PPAR)在脂肪组织中优先表达，其中 它负责协调脂肪细胞的基因表达和 差异化。脂肪细胞是能量的重要组成部分。 脊椎动物的平衡；提供充足的能量 按需预留。脂肪组织过度发育 导致肥胖，这是非胰岛素的一个重要风险因素- 依赖型糖尿病和一些心血管疾病。 已知脂肪酸，如花生四烯酸(AA)可诱导 脂肪生成，但它们的作用机制尚不清楚。最近， AA代谢产物15-脱氧-β-12，14-前列腺素J2(15d-PGJ2) 已被证明是PPAR伽马的配体。15d-PGJ2是否为 PPAR伽马的生理相关配体尚不确定，因此 增加了其他类脂代谢物作为 PPAR-γ的内源性配体。因此，其主要目标是 本研究建议确定PPAR的内源性配体(S) 并研究其生理生化介体。 他们的释放。具体目标包括：1；对 3T3-F442a前脂肪细胞中的主要脂肪酸/代谢物。2. 刺激PPARγ和PPARγ的脂肪酸/代谢物的阐明 诱导脂肪细胞分化。3.关于是否 已知可诱导脂肪细胞分化的激动剂(例如。IGF-1， 糖皮质激素)，通过释放内源激素发挥作用 脂肪酸/代谢物，如果是的话，研究第二信使 他们使用的系统。

The nuclear hormone receptor, peroxisome proliferator activated receptor gamma (PPAR gamma) is expressed preferentially in adipose tissue, where it is responsible for coordinating adipocyte gene expression and differentiation. Adipocytes are an important component of the energy equilibrium of vertebrate organisms; providing an abundant energy reserve upon demand. The excessive development of adipose tissue results in obesity, which is a significant risk factor for non-insulin- dependent diabetes mellitus and a number of cardiovascular diseases. Fatty acids, such as arachidonic acid (AA) are known to induce adipogenesis, however their mechanism of action is not known. Recently, an AA metabolite, 15-deoxy-delta-12,14-prostaglandin J2 (15d-PGJ2), has been shown to be a ligand for PPAR gamma. Whether 15d-PGJ2 is the physiologically relevant ligand for PPAR gamma is not certain and thus raises the possibility that other lipid metabolites may serve as endogenous ligands for PPAR gamma. Therefore, the primary objective of this research proposal is to determine endogenous ligand(s) for PPAR gamma and to investigate the physiological and biochemical mediators of their release. The specific aims involve: 1; Characterization of the major fatty acids/metabolites in 3T3-F442A preadipocytes. 2. Elucidation of the fatty acids/metabolites that stimulate PPAR gamma and induce adipocyte differentiation. 3. Determination as to whether agonists known to induce adipocyte differentiation (eg. IGF-1, glucocorticoids), exert their actions via the release of endogenous fatty acids/metabolites, and if so investigate the second messenger systems they employ.