Cell surface receptors, nuclear receptors and ligands that regulate adipose tissue development

Our knowledge of adipose tissue development has increased dramatically over the last two decades, through a combination of in vitro studies using cellular models and in vivo studies using mouse models with invalidated target genes. Critical early events of the differentiation programme appear to involve in preadipose cells (i) the entry of fatty acids and the production of fatty acid metabolites as activators/ligands of nuclear peroxisome proliferator-activated receptors (PPARs) and (ii) the very early expression of PPARdelta and CAAT/enhancer binding proteins (C/EBPs) beta and delta. Among fatty acids, prostacyclin produced from arachidonic acid enhances the expression of both C/EBPs through cell surface IP receptor and presumably activates PPARdelta. Together, these transcription factors up-regulate the expression of PPARgamma and C/EBPalpha which lead in turn to the acquisition of the adipocyte phenotype. Altogether, these studies have provided a molecular link between high-fat diets and excess of adipose tissue development through hyperplasia and hypertrophy.