Regulation of adipocyte gene expression by polyunsaturated fatty acids

A wide number of adipocyte genes are regulated by exogenous polyunsaturated fatty acids (PUFA) through the actions of the peroxisome proliferator activated receptor. Such genes include the adipocyte lipid-binding protein (ALBP or aP2) which plays a central role in facilitating the trafficking of fatty acids within adipocytes. Work from a number of laboratories has suggested the key elements of the lipid signal transduction pathway include: (1) the transport of exogenous PUFAs across the plasma membrane, (2) metabolism of polyunsaturated fatty acids to second messengers including 15-deoxy Δ^12,14 prostaglandin J₂ (15dPGJ₂), (3) trafficking of 15dPGJ₂ and other second messengers from the smooth ER to the nucleus for association with peroxisome proliferator activated receptorγ (PPARγ), and (4) dimerization of PPARγ with retinoid X receptor (RXR) permitting regulation of transcription via association with any of several nuclear co-activators or repressors. In addition to the aP2 gene being a target of activation by fatty acids, at the protein level ALBP/aP2 plays a role in trafficking of fatty acids and/or their metabolises. We report here that in a heterologous system using CV-1 cells transiently transfected with PPARγ2, co-expression of ALBP/aP2 enhances the PPAR-dependent activation of gene transcription. These results suggest that ALBP/aP2 functions as a positive factor in fatty acid signalling by directly targetting and delivering fatty acids metabolites to the lipid signal transduction pathway.