COUNTERACTION OF RETINOIC ACID AND 1,25-DIHYDROXYVITAMIN-D3 ON UP-REGULATION OF ADIPOCYTE DIFFERENTIATION WITH PPAR-GAMMA LIGAND, AN ANTIDIABETIC THIAZOLIDINEDIONE, IN 3T3-L1 CELLS

Retinoic acid (RA) and 1,25-dihydroxyvitamin D3 (1,25 (OH)2 D3) inhibi ted adipocyte differentiation of 3T3-L1 preadipocytes in the presence of thiazolidinedione, a specific ligand for peroxisome proliferator-ac tivated receptor gamma (PPAR gamma). These fat-soluble vitamins repres sed the upregulated protein expression of PPAR gamma 2 during the firs t 40 hours of initiation of 3T3-L1 Compared with RA, 1,25 (OH)2 D3 inh ibited PPAR gamma 2 expression more effectively and caused concomitant ly a greater inhibition of adipocyte differentiation. These results su ggest that the inhibitory action of adipocyte differentiation by RA or 1,25 (OH)2 D3 is exhibited through direct repression of the expressio n of PPAR gamma 2 protein, even in the presence of its They also raise the intriguing possibility that attenuation or amplification of the p harmacological effects of thiazolidinedione that are dependent on PPAR gamma in adipose cells is caused by alteration of the levels of these fat-soluble vitamins. (C) 1998 Elsevier Science Inc.