Derosa Giuseppe, Sahebkar Amirhossein, Maffioli Pamela
Department of Internal Medicine and Therapeutics, Centre of Diabetes and Metabolic Diseases, University of Pavia and Fondazione IRCCS Policlinico S. Matteo, Pavia, Italy.
Laboratory of Molecular Medicine, University of Pavia, Pavia, Italy.
J Cell Physiol. 2018 Jan;233(1):153-161. doi: 10.1002/jcp.25804. Epub 2017 Mar 27.
Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors involved in several physiological processes including modulation of cellular differentiation, development, metabolism of carbohydrates, lipids, proteins, and tumorigenesis. The aim of this review is to examine how different PPAR ligands act, and discuss their use in clinical practice. PPAR ligands have a lot of effects and applications in clinical practice. Some PPAR ligands such as fibrates (PPAR-α ligands) are currently used for the treatment of dyslipidemia, while pioglitazone and rosiglitazone (PPAR-γ ligands) are anti-diabetic and insulin-sensitizing agents. Regarding new generation drugs, acting on both α/γ, β/δ, or α/δ receptors simultaneously, preliminary data on PPAR-α/γ dual agonists revealed a positive effect on lipid profile, blood pressure, atherosclerosis, inflammation, and anti-coagulant effects, while the overexpression of PPAR-β/δ seems to prevent obesity and to decrease lipid storage in cardiac cells. Finally, PPAR-α/δ dual agonist induces resolution of nonalcoholic steatohepatitis without fibrosis worsening.
过氧化物酶体增殖物激活受体（PPARs）是配体激活的转录因子，参与多种生理过程，包括调节细胞分化、发育、碳水化合物、脂质、蛋白质代谢以及肿瘤发生。本综述的目的是研究不同的PPAR配体如何发挥作用，并讨论它们在临床实践中的应用。PPAR配体在临床实践中有许多作用和应用。一些PPAR配体，如贝特类药物（PPAR-α配体）目前用于治疗血脂异常，而吡格列酮和罗格列酮（PPAR-γ配体）是抗糖尿病和胰岛素增敏剂。关于同时作用于α/γ、β/δ或α/δ受体的新一代药物，PPAR-α/γ双重激动剂的初步数据显示对血脂谱、血压、动脉粥样硬化、炎症和抗凝作用有积极影响，而PPAR-β/δ的过表达似乎可预防肥胖并减少心肌细胞中的脂质储存。最后，PPAR-α/δ双重激动剂可诱导非酒精性脂肪性肝炎消退而不会使纤维化恶化。
