Carotenoids and retinoids as suppressors on adipocyte differentiation via nuclear receptors.

The adipocyte differentiation program is regulated by the sequential expression of transcriptional activators, mainly peroxisome proliferator activated receptor (PPAR) families. In the present study, we have decided to systematically examine the effects of vitamin A and its precursors, carotenoids and retinoids, on terminal differentiation from preadipocytes to adipocytes on the cellular and molecular aspects. The effects of active form of vitamin A, retinoic acid (RA), are believed to be mediated by specific nuclear receptor proteins [retinoic acid receptor (RAR)] which are members of the steroid and thyroid/retinoid receptor superfamily of ligand dependent transcriptional regulators, RARalpha, RARgamma, RXRalpha, and RXRbeta mRNA were abundant in adipose tissue and 3T3-L1 adipose cells. The autoregulated amplification of RARgamma mRNA was observed by these own ligands in 3T3-L1 cells. And, RA inhibited PPARgamma2 expression more effectively and caused concomitantly a greater inhibition of adipocyte differentiation. These results suggest that the inhibitory action of adipocyte differentiation by carotenoids and retinoids are exhibited through the RAR up-regulation and the suppression of PPARgamma2. The nature of the cross talk of vitamin A actions between the RARs, RXRs and PPARs via co-activator in adipose tissue will likely prove to be important for understanding the process of adipogenesis.