Peroxisome proliferator-activated receptors and their ligands: nutritional and clinical implications--a review.
Peroxisome proliferator-activated receptors and their ligands: nutritional and clinical implications--a review.
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DOI：
10.1186/1475-2891-13-17
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发表时间：
2014-02-14
影响因子：
5.4
通讯作者：
Grygiel-Górniak B
中科院分区：
文献类型：
--
作者：
Grygiel-Górniak B
过氧化物酶体增殖物激活受体在许多组织中表达，包括脂肪细胞、肝细胞、肌肉和内皮细胞;然而，亲和力取决于过氧化物酶体增殖物激活受体的同种型以及不同的分布和表达谱，这最终导致不同的临床结果。因为它们在脂质和葡萄糖的稳态中起着重要作用，所以它们被称为脂质和胰岛素传感器。它们的作用仅限于特定的组织类型，因此揭示了对靶细胞的特征性影响。PPARα主要影响脂肪酸代谢，其活化降低脂质水平，而PPARγ主要参与脂肪形成、能量平衡和脂质生物合成的调节。PPARβ/δ参与脂肪酸氧化，主要在骨骼肌和心肌中，但它也调节血糖和胆固醇水平。许多天然和合成配体影响这些受体的表达。合成配体广泛用于治疗血脂异常（例如贝特类- PPARα激活剂）或糖尿病（例如噻唑烷二酮类- PPARγ激动剂）。新一代药物-- PPARα/γ双重激动剂--显示出降血脂、消肿、抗动脉粥样硬化、抗炎和抗凝作用，而PPARβ/δ的过表达可防止肥胖的发展，并减少心肌细胞中的脂质积聚，即使在高脂肪饮食期间也是如此。关于天然PPAR激动剂对葡萄糖和脂质代谢的表达和功能的精确数据仍然缺失，主要是因为相同的配体影响几种受体，并且许多报告提供了相互矛盾的结果。迄今为止，我们知道PPARs具有容纳和结合各种天然和合成亲脂性酸的能力，如必需脂肪酸、类花生酸、植烷酸和棕榈酰乙醇酰胺。本文概述了PPARs的作用、分子机制以及这些受体在营养和治疗中的作用。
Peroxisome proliferator-activated receptors are expressed in many tissues, including adipocytes, hepatocytes, muscles and endothelial cells; however, the affinity depends on the isoform of PPAR, and different distribution and expression profiles, which ultimately lead to different clinical outcomes. Because they play an important role in lipid and glucose homeostasis, they are called lipid and insulin sensors. Their actions are limited to specific tissue types and thus, reveal a characteristic influence on target cells. PPARα mainly influences fatty acid metabolism and its activation lowers lipid levels, while PPARγ is mostly involved in the regulation of the adipogenesis, energy balance, and lipid biosynthesis. PPARβ/δ participates in fatty acid oxidation, mostly in skeletal and cardiac muscles, but it also regulates blood glucose and cholesterol levels. Many natural and synthetic ligands influence the expression of these receptors. Synthetic ligands are widely used in the treatment of dyslipidemia (e.g. fibrates - PPARα activators) or in diabetes mellitus (e.g. thiazolidinediones - PPARγ agonists). New generation drugs - PPARα/γ dual agonists - reveal hypolipemic, hypotensive, antiatherogenic, anti-inflammatory and anticoagulant action while the overexpression of PPARβ/δ prevents the development of obesity and reduces lipid accumulation in cardiac cells, even during a high-fat diet. Precise data on the expression and function of natural PPAR agonists on glucose and lipid metabolism are still missing, mostly because the same ligand influences several receptors and a number of reports have provided conflicting results. To date, we know that PPARs have the capability to accommodate and bind a variety of natural and synthetic lipophilic acids, such as essential fatty acids, eicosanoids, phytanic acid and palmitoylethanolamide. A current understanding of the effects of PPARs, their molecular mechanisms and the role of these receptors in nutrition and therapeutic treatment are delineated in this paper.
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DOI：
10.1073/pnas.95.15.8806
发表时间：
1998-07-21
影响因子：
11.1
作者：
Elstner, E;Müller, C;Koeffler, HP
通讯作者：
Koeffler, HP
影响因子：
7.7
作者：
Carmona, Maria Carmen;Louche, Katie;Penicaud, Luc
通讯作者：
Penicaud, Luc
影响因子：
16.2
作者：
Forsblom C;Hiukka A;Leinonen ES;Sundvall J;Groop PH;Taskinen MR
通讯作者：
Taskinen MR
DOI：
10.1056/nejmoa1001282
发表时间：
2010-04-29
期刊：
The New England journal of medicine
影响因子：
--
作者：
ACCORD Study Group;Ginsberg HN;Elam MB;Lovato LC;Crouse JR 3rd;Leiter LA;Linz P;Friedewald WT;Buse JB;Gerstein HC;Probstfield J;Grimm RH;Ismail-Beigi F;Bigger JT;Goff DC Jr;Cushman WC;Simons-Morton DG;Byington RP
通讯作者：
Byington RP
DOI：
10.1186/1476-5926-2-3
发表时间：
2003-01-31
期刊：
Comparative hepatology
影响因子：
--
作者：
Boitier, Eric;Gautier, Jean-Charles;Roberts, Ruth
通讯作者：
Roberts, Ruth