What is the primary mechanism of action of fibrates?

Fibrates primarily exert their effects through the activation of peroxisome proliferator-activated receptors (PPARs), specifically the PPAR-alpha subtype. This nuclear receptor plays a crucial role in lipid metabolism. When fibrates bind to PPAR-alpha, they facilitate the transcription of genes involved in fatty acid oxidation, leading to an increase in the breakdown of triglycerides. This mechanism also results in a reduction in triglyceride levels and an increase in high-density lipoprotein (HDL) cholesterol, which has a protective effect against cardiovascular diseases.

By activating PPARs, fibrates also modulate the expression of apolipoproteins, significantly lowering levels of apolipoprotein C-III, which inhibits lipoprotein lipase. This could further enhance triglyceride clearance from the bloodstream. This multifaceted mechanism highlights the importance of PPAR activation in lipid homeostasis and underscores why this option accurately represents the primary action of fibrates.