脂代谢失衡引起脂肪过度沉积，导致肥胖。NAD+依赖的组蛋白去乙酰化酶SIRT1可多路径调控脂代谢，已成为肥胖及肥胖相关疾病防治靶点。初步研究显示，叶黄素具有调节脂代谢防治肥胖的潜力且能激活SIRT1，但叶黄素通过SIRTI1信号途径如何调控脂代谢机制未明。本项目拟通过对高脂膳食诱导和转基因肥胖模型大鼠进行叶黄素干预，分析SIRT1变化对脂代谢和脂肪细胞分化关键调节因子PGC-1α、PPARα/γ、FOXO、SREBP1c等的影响，及对这些因子调控的脂肪酸合成关键酶（ACC、FAS、SCD1）、脂肪酸分解关键酶、脂肪酸摄取关键酶（LPL）、脂肪细胞分化及棕色化关键分子、与脂肪酸氧化有关的线粒体生成关键分子（NRF1、TFAM）等的影响，以阐明叶黄素基于SIRT1信号通路调控脂代谢改善脂肪沉积的相关机制。此项目的实施和相关成果取得可为肥胖及肥胖相关疾病防治提供积极有效的分子靶点和新的膳食策略。

Lipid metabolism dysfunction leads to excess fatty deposits (obesity). SIRT1, NAD+-dependent histone deacetylase, has become an attractive target to prevent obesity and obesity-related diseases due to regulating lipid metabolism via mulitiple signal pathways. Previous researches show that lutein is the potential phytochemical for the prevention and treatment of obesity likely by lipid metabolism regulation and has the ability to activate SIRT1, but the detail effects and mechanisms mediated by SIRT1 pathway has not yet been elucidated. In this project, obese rats model induced by high-fat diet or transgenic method are supplemented with lutein and/or SIRT1 inhibitor. After treatments, the expresssions of SIRT1 and the SIRT1-related regulatory factors which play vital role in lipid metabolism and adipocyte differentiation such as PGC-1α、PPARα/γ、FOXO、SREBP1c are analyzed. Further, these regulatory factors’ down-stream key moleculars and enzymes involving lipogenesis (ACC, FAS, SCD1), lipid mobilization (ATGL、HSL、CPT1α、ACOX1、FAT/CD36、UCP1/3), fatty acid uptake from circulating triacylglycerols (LPL), adipocyte differentiation and browning (C/EBPα/β、PRDM16、UCP1) and mitochondriopoiesis (NRF1、TFAM), are examined in the level of mRNA, protein or enzyme activities. Finally, the ameliorative effect of lutein on fatty-deposits and the underlying mechanisms by which lutein promote lipid metabolism via multiple SIRT1-associated signaling pathways will be revealed. The results of this study will provide an effective target and new dietary strategy for the prevention and treatment of obesity and obesity-related diseases.