Open AccessPPARS - Peroxisome Proliferator Activated Receptor Activators and Fibrates Actions
Author(s) -
Sidney Carvalho Fernandes,
Anita L R Saldanha,
Ana Paula Pantoja Margeotto,
André Luiz Valera Gasparoto,
Tânia Leme da Rocha Martinez
Publication year - 2021
Publication title -
journal of medical-clinical research and reviews
Language(s) - English
Resource type - Journals
ISSN - 2639-944X
DOI - 10.33425/2639-944x.1194
Subject(s) - peroxisome proliferator activated receptor , gemfibrozil , bezafibrate , clofibrate , receptor , chemistry , peroxisome proliferator activated receptor alpha , endocrinology , pharmacology , medicine , nuclear receptor , fibrate , biochemistry , statin , cholesterol , transcription factor , gene
Peroxisome Proliferator Activated Receptor sits part of the family of nuclear receptors, which has about 50 known receptors, including thyroid hormone receptors, which have the function of regulating metabolism and metabolizing and eliminating substances. These receptors, to act, must be activated by ligands, form a heterodmer with the retinoic acid receptor, recruit activating cofactors, release inhibitory cofactors to which they are bound, and then act on the responsive element of target gene. Three species of peroxisome proliferator activated receptor are known: PPARa, PPARγ and PPARβ (also known as PPARd or β/d). The prototypes of PPARa activators are the derivatives of fibricacid, of which the first representative was clofibrate, used as a lipid-lowering factor in the 1960s and 1970s. Although there may be a small variation among the various fibrates regarding the mechanism of action, these drugs are basically PPARa activators. In the action of fibrates, there is a reduction of triglycerides, with a decrease in the synthesis of VLDL, increase of HDL particles and transformation of small and dense LDL into larger, less dense LDL and with lower atherogenic potential. Fibrates are second-choice substances, and statins are the first for the treatment of hypertriglyceridemia. Fibrates are efficient for the treatment of patients with low HDL-C, decrease macro and microvascular disease of diabetic patients. The recommendation is do not associate gemfibrozil with statins. Other fibrates may be associated, and preference should be given to the association of statins that are not metabolized by CYP3A4: rosvastatin, pravastatin and fluvastatin.