Role of PPARS and LXRs in mechanisms explaining the effects of different dietary components on lipid metabolism

近年来，膳食脂肪被认为不仅仅是能量的来源。现在人们了解到，脂肪酸和胆固醇可能通过涉及特定核系统的方式影响基因表达，这些核系统被称为过氧化物酶体增殖物激活受体(PPAR)和肝脏X受体(LXR)。这些受体已被证明可以调节脂肪酸和甾醇对脂肪代谢的影响，从而可能影响个人患心脏病和肥胖的风险。PPAR可调节脂肪代谢，包括脂肪酸氧化、脂肪细胞发育、脂蛋白代谢和葡萄糖稳态。LXRs已被证明可以调节胆固醇的吸收、外周细胞胆固醇的外流和极低密度脂蛋白的代谢。然而，PPAR和LXRs之间可能的联系，以及它们在调节饮食成分类型对脂代谢的影响方面的作用，仍有待探索。此外，在植物中发现的脂肪酸和甾醇(植物甾醇)被认为影响重要的食欲调节剂瘦素和生长激素的产生。本研究的总体目标是使用体外和体内模型来研究PPAR和LXRs之间的联系，以及它们在调节不同饮食成分对脂肪代谢和食欲调节方面的作用。为了达到规定的目标，体外实验将使用现代遗传图谱分析来检查已知和未知的脂代谢基因对不同饮食制剂的反应。在该计划的第二部分，将使用在最初的一系列基于细胞的实验中发现的差异表达的基因，在小鼠模型中研究定性脂肪和类固醇消耗在调节脂肪途径中的作用。预计拟议的一系列实验的结果将使创新的营养/药物方法能够改善加拿大人的心脏病和肥胖症患病率。本研究的目的是使用体外和体内模型来研究PPAR和LXR之间的联系及其在调节不同饮食成分对脂代谢的影响方面的作用。

In recent years, dietary lipids have been considered more than just sources of energy. It is now understood that fatty acids and cholesterol may affect gene expression in ways that involve specific nuclear systems termed peroxisome proliferator-activated receptors (PPAR) and liver X receptors (LXR). These receptors have been shown to mediate effects of both fatty acids and sterols on lipid metabolism in ways that may affect and individual risk for heart disease and obesity. PPARs have been shown to regulate lipid metabolism including fatty acid oxidation, fat cell development, lipoprotein metabolism and glucose homeostasis. LXRs have been shown to regulate cholesterol absorption, efflux of cholesterol from peripheral cells and metabolism of VLDL. However, possible linkages between PPARs and LXRs, as well as their role in regulating the effect of type of dietary components on lipid metabolism, have yet to be explored. In addition, fatty acids and sterols found in plants (phytosterols) are thought to affect the production of important appetite regulators leptin and ghrelin. The global objective of the present study is to use both in vitro and in vivo models to investigate links between PPARs and LXRs and their role in regulating the effect of different dietary components on lipid metabolism and appetite regulation. To achieve the stated objectives, the in vitro experiments will examine the response to different dietary agents of both known and unknown genes of lipid metabolism using modern genetic profiling analyses. In the second part of the program the role of qualitative fat and sterol consumption will be examined in the regulation of lipid pathways in a mouse model using genes found to be differentially expressed in the initial series of cell-based experiments. It is anticipated that results from the proposed series of experiments should enable innovative nutraceutical/pharmaceutical approaches to improving heart disease and obesity prevalence of Canadians.objective of the present study is to use both in vitro and in vivo models to investigate links between PPARs and LXRs and their role in regulating the effect of different dietary components on lipid metabolism.