肥胖是机体脂肪含量过多而引起的慢性代谢性疾病。脂肪细胞是能量储存的重要细胞，其脂代谢受到众多营养物质,信号分子和miRNA的调节。这些调控通路的异常可导致脂肪细胞的脂代谢紊乱和肥胖的发生。本项目以脂肪细胞的脂代谢为中心，深入探讨和阐明营养分子如脂肪酸、信号转导途径以及miRNAs对脂肪细胞内脂类的摄取，合成，储存，分解和氧化的调控机制，以及脂肪细胞脂代谢异常导致肥胖发生的机理。研究内容包括：1）阐明Fsp27和Rab18受营养和信号调控的机制及其在脂肪细胞脂代谢和肥胖发生中的作用； 2）系统筛选营养物质（脂肪酸）和信号通路（cAMP-PKA, 胰岛素, AMPK及mTOR）对脂肪细胞内参与脂代谢的重要蛋白的乙酰化或磷酸化修饰及其对脂代谢的影响；3) 阐明miR-145, 106和 708调节脂肪细胞脂代谢的分子机制及其生理病理功能。该项目的实施将为肥胖的防治提供理论基础和重要靶点。

Obesity represents excess lipid storage in adipose tissue and has been associated with the development of other metabolic disorders. The amount of lipid storage in adipose tissue is the result of coordinated regulation of multiple lipid metabolic pathways and is controlled by nutrient supply, signal transduction pathways and miRNAs. The objective of this proposal is to understand the underlying molecular mechanism of nutrient, signaling and specific miRNAs in controlling lipid metabolic pathways in adipocytes and their role in modulating obesity development. Specific research plans include: 1) To elucidate the role of Fsp27 and Rab18, two lipid droplet associated proteins, in mediating fatty acid and cAMP-PKA regulated lipid metabolism in adipocytes; 2) To systematically screen for downstream targets that are regulated by fatty acid treatment and various signaling pathways and control lipid metabolism in adipocytes; 3) To delineate the molecular pathways by which miRNAs (miRNA-145, 106 and 708) control adipocyte lipid metabolism and the development of obesity. Understanding the mechanism of nutrient sensing, signal transduction and miRNA in controlling lipid metabolism would greatly aid in the designing of therapeutical drugs for the prevention and treatment of obesity and its associated diseases.