Varga Tamas, Czimmerer Zsolt, Nagy Laszlo
Department of Biochemistry and Molecular Biology, Research Center for Molecular Medicine, University of Debrecen, Medical and Health Science Center, Hungary.
Biochim Biophys Acta. 2011 Aug;1812(8):1007-22. doi: 10.1016/j.bbadis.2011.02.014. Epub 2011 Mar 5.
Cells are constantly exposed to a large variety of lipids. Traditionally, these molecules were thought to serve as simple energy storing molecules. More recently it has been realized that they can also initiate and regulate signaling events that will decisively influence development, cellular differentiation, metabolism and related functions through the regulation of gene expression. Multicellular organisms dedicate a large family of nuclear receptors to these tasks. These proteins combine the defining features of both transcription factors and receptor molecules, and therefore have the unique ability of being able to bind lipid signaling molecules and transduce the appropriate signals derived from lipid environment to the level of gene expression. Intriguingly, the members of a subfamily of the nuclear receptors, the peroxisome proliferator-activated receptors (PPARs) are able to sense and interpret fatty acid signals derived from dietary lipids, pathogenic lipoproteins or essential fatty acid metabolites. Not surprisingly, Peroxisome proliferator-activated receptors were found to be key regulators of lipid and carbohydrate metabolism. Unexpectedly, later studies revealed that Peroxisome proliferator-activated receptors are also able to modulate inflammatory responses. Here we summarize our understanding on how these transcription factors/receptors connect lipid metabolism to inflammation and some of the novel regulatory mechanisms by which they contribute to homeostasis and certain pathological conditions. This article is part of a Special Issue entitled: Translating nuclear receptors from health to disease.
细胞不断暴露于种类繁多的脂质中。传统上，这些分子被认为只是简单的能量储存分子。最近人们认识到，它们还能启动和调节信号转导事件，通过调控基因表达来决定性地影响发育、细胞分化、代谢及相关功能。多细胞生物为此专门配备了一大类核受体来执行这些任务。这些蛋白质兼具转录因子和受体分子的典型特征，因而具有独特的能力，能够结合脂质信号分子，并将源自脂质环境的适当信号传递到基因表达层面。有趣的是，核受体亚家族中的过氧化物酶体增殖物激活受体（PPARs）能够感知并解读源自膳食脂质、致病性脂蛋白或必需脂肪酸代谢产物的脂肪酸信号。不出所料，过氧化物酶体增殖物激活受体被发现是脂质和碳水化合物代谢的关键调节因子。出乎意料的是，后来的研究表明，过氧化物酶体增殖物激活受体还能够调节炎症反应。在此，我们总结了对这些转录因子/受体如何将脂质代谢与炎症联系起来的理解以及它们有助于维持体内稳态和某些病理状态的一些新型调节机制。本文是名为“将核受体从健康转化为疾病”的特刊的一部分。
