Counteraction of retinoic acid and 1,25-dihydroxyvitamin D3 on up-regulation of adipocyte differentiation with PPARγ ligand, an antidiabetic thiazolidinedione, in 3T3-L1 cells

Retinoic acid (RA) and 1,25-dihydroxyvitamin D3 (1,25 (OH)2 D3) inhibited adipocyte differentiation of 3T3-L1 preadipocytes in the presence of thiazolidinedione, a specific ligand for peroxisome proliferator-activated receptor gamma (PPAR gamma). These fat-soluble vitamins repressed the upregulated protein expression of PPAR gamma 2 during the first 40 hours of initiation of 3T3-L1 Compared with RA, 1,25 (OH)2 D3 inhibited PPAR gamma 2 expression more effectively and caused concomitantly a greater inhibition of adipocyte differentiation. These results suggest that the inhibitory action of adipocyte differentiation by RA or 1,25 (OH)2 D3 is exhibited through direct repression of the expression of PPAR gamma 2 protein, even in the presence of its They also raise the intriguing possibility that attenuation or amplification of the pharmacological 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.