REGULATION OF ADIPOCYTE GENE-EXPRESSION BY POLYUNSATURATED FATTY-ACIDS

A wide number of adipocyte genes are regulated by exogenous polyunsatu rated fatty acids (PUFA) through the actions of the peroxisome prolife rator activated receptor. Such genes include the adipocyte lipid-bindi ng protein (ALBP or aP2) which plays a central role in facilitating th e trafficking of fatty acids within adipocytes. Work from a number of laboratories has suggested the key elements of the lipid signal transd uction pathway include: (I) the transport of exogenous PUFAs across th e plasma membrane, (2) metabolism of polyunsaturated fatty acids to se cond messengers including 15-deoxy Delta(12,14) prostaglandin J(2) (15 dPGJ(2)), (3) trafficking of 15dPGJ(2) and other second messengers fro m the smooth ER to the nucleus for association with peroxisome prolife rator activated receptor gamma (PPAR gamma), and (4) dimerization of P PAR gamma with retinoid X receptor (RXR) permitting regulation of tran scription 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 traffick ing of fatty acids and/or their metabolises, We report here that in a heterologous system using CV-1 cells transiently transfected with PPAR gamma 2, co-expression of ALBP/aP2 enhances the PPAR-dependent activa tion of gene transcription. These results suggest that ALBP/aP2 functi ons as a positive factor in fatty acid signalling by directly targetti ng and delivering fatty acids metabolites to the lipid signal transduc tion pathway.