Modulación del PPARα por agentes farmacológicos y naturales y sus implicaciones metabólicas

Peroxisome proliferator-activated receptor alpha (PPARα) binds fatty acids, eicosanoids, or fibrates, and regulates transcription of genes involved both in lipid and glucose metabolism as well as in inflammation. Fibrates are PPARα ligands used to normalize lipid and glucose parameters and exert anti-inflammatory effects. In fact, fibrates have already been demonstrated to benefit metabolic syndrome, type 2 diabetes and cardiovascular diseases. This article reviews the mechanism of action and the functional roles of fibrates, emphasising the factors modulating their capacity to activate PPARα and affecting their effectiveness. These factors would possibly explain the findings obtained in animal studies and clinical trials with fibrates which showed either untoward effects and/or inefficient hypolipidemic action of PPARα activation. Therefore, all those findings have underlined the need to search for pharmacological or nutritional solutions based on modulation of PPARα. This strategy could either be complementary to or replace the classical therapy. Thus, a brief survey of the natural and synthetic agonists of PPARα, more specific, selective, with higher potency and, supposedly, displaying greater effectiveness and fewer adverse effects than fibrates which are currently being developed, is also mentioned.