Molecular properties of fatty acids related to PPAR binding and metabolic diseases

Abstract

Peroxisome proliferator-activated receptor (PPAR) is a class of nuclear receptors responsible for the transcription of genes that regulate the metabolism of carbohydrates and lipids. The main endogenous ligands of PPARs are fatty acids, leukotrienes and derivatives. The PPAR family has three isoforms: α, γ, and δ. To understand the main interactions responsible for the PPAR selectivity of a subset of ligands, we performed molecular modeling studies on a set of 16 fatty acids. From the results obtained, we found that stereochemical, hydrophobic, and polar properties are correlated with PPAR selectivity and can be used to design new ligands with improved biological selectivity.