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

近年来，膳食脂质被认为不仅仅是能量的来源。现在了解到脂肪酸和胆固醇可能影响基因表达的方式涉及特定的核系统，称为过氧化物酶体增殖激活受体（PPAR）和肝X受体（LXR）。研究表明，这些受体介导脂肪酸和甾醇对脂质代谢的影响，可能影响心脏病和肥胖的个体风险。ppar已被证明可以调节脂质代谢，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、外周细胞的胆固醇外排和VLDL的代谢。然而，ppar和LXRs之间的可能联系，以及它们在调节膳食成分类型对脂质代谢的影响中的作用，还有待探索。此外，在植物中发现的脂肪酸和甾醇（植物甾醇）被认为会影响重要的食欲调节剂瘦素和饥饿素的产生。本研究的总体目标是利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膳食成分对脂质代谢和食欲调节作用中的作用。为了达到既定目标，体外实验将使用现代基因谱分析来研究已知和未知的脂质代谢基因对不同膳食制剂的反应。在节目的第二部分，定性脂肪和甾醇消耗的作用将检查在调节脂质途径的小鼠模型中，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。预计，拟议的一系列实验的结果将使创新的营养/制药方法能够改善加拿大人的心脏病和肥胖症患病率。本研究的目的是通过体外和体内模型研究ppar和LXRs之间的联系，以及它们在调节不同膳食成分对脂质代谢的影响中的作用。

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.