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过氧化物酶体增殖物激活受体(PPARS)在脂质调节和炎症控制中的作用

[Role of the peroxisome proliferator-activated receptors (PPARS) in the regulation of lipids and inflammation control].

作者信息

Bocher Virginie, Chinetti Giulia, Fruchart Jean-Charles, Staels Bart

机构信息

UR 545 INSERM, Département d'Athérosclérose, Institut Pasteur de Lille, 1, rue Calmette, 59019 Lille et Faculté de Pharmacie, Université de Lille II, 59006 Lille, France.

出版信息

J Soc Biol. 2002;196(1):47-52.

Abstract

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors belonging to the nuclear receptor family. The hypolipidemic fibrates and the antidiabetic glitazones are synthetic ligands for PPAR alpha and PPAR gamma, respectively. Furthermore, fatty acids and eicosanoids are natural PPAR ligands. PPARs function as regulators of lipid and lipoprotein metabolism and glucose homeostasis and influence cellular proliferation, differentiation and apoptosis. PPAR alpha is highly expressed in tissues such as liver, muscle, kidney and heart, where it stimulates the beta-oxidative degradation of fatty acids. PPAR alpha furthermore mediates the action of the hypolipidemic drugs of the fibrate class on plasma lipoprotein metabolism. PPAR gamma is predominantly expressed in intestine and adipose tissue. PPAR gamma triggers adipocyte differentiation and promotes lipid storage. In addition, PPARs play a role in inflammation control. PPAR activators inhibit the activation of inflammatory response genes by negatively interfering with the NF-kappa B and AP-1 signalling pathways. PPAR activators exert these anti-inflammatory activities in different immunological and vascular wall cell types such as monocyte-macrophages, endothelial, epithelial and smooth muscle cells in which PPARs are expressed. These findings indicate a modulatory role for PPARs in the control of the inflammatory response with potential therapeutic applications in inflammation-related diseases, such as atherosclerosis.

摘要

过氧化物酶体增殖物激活受体(PPARs)是属于核受体家族的配体激活转录因子。降血脂的贝特类药物和抗糖尿病的格列酮类药物分别是PPARα和PPARγ的合成配体。此外,脂肪酸和类二十烷酸是天然的PPAR配体。PPARs作为脂质和脂蛋白代谢以及葡萄糖稳态的调节因子,影响细胞增殖、分化和凋亡。PPARα在肝脏、肌肉、肾脏和心脏等组织中高表达,在这些组织中它刺激脂肪酸的β氧化降解。PPARα还介导贝特类降血脂药物对血浆脂蛋白代谢的作用。PPARγ主要在肠道和脂肪组织中表达。PPARγ触发脂肪细胞分化并促进脂质储存。此外,PPARs在炎症控制中发挥作用。PPAR激活剂通过负面干扰NF-κB和AP-1信号通路来抑制炎症反应基因的激活。PPAR激活剂在不同的免疫和血管壁细胞类型(如单核细胞-巨噬细胞、内皮细胞、上皮细胞和平滑肌细胞,这些细胞中表达PPARs)中发挥这些抗炎活性。这些发现表明PPARs在炎症反应控制中具有调节作用,在动脉粥样硬化等炎症相关疾病中具有潜在的治疗应用。

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