THE PREVENTION OF ADIPOSE DIFFERENTIATION OF 3T3-L1 CELLS CAUSED BY RETINOIC ACID IS ELICITED THROUGH RETINOIC ACID RECEPTOR-ALPHA

Retinoids, especially all-trans retinoic acid (RA), have been shown to inhibit the differentiation of preadipose cells. It is important to h uman health, especially to obesity, that the regulatory system for the differentiation of adipocytes is well defined. Previously, we have sh own that retinoic acid receptor (RAR) gamma 2 gene expression is up-re gulated by RA in 3T3-L1 preadipose cells. In this study, the RAR syste m was dissected and the RA-regulated function in 3T3-L1 cells was assi gned to one given receptor. We used three synthetic retinoids; (1) Ro 41-5253, a selective RAR alpha antagonist, (2) Ch 55, an RAR alpha, be ta and gamma agonist, and (3) Am 80, an RAR a and P agonist, which has less affinity to RAR gamma. Ro 41-5253 reverted RA-induced inhibition of the differentiation of 3T3-L1 cells. However, there was no signifi cant reversion in RA-induced RAR gamma mRNA level by treatment with Ro 41-5253, In the case of RAR agonists, both Am 80 and Ch 55 strongly i nhibited the differentiation of 3T3-L1 cells. However, Am 80 weakly in creased RAR gamma mRNA content less than did Ch 55. These findings sug gest, that RAR alpha is involved in the prevention of adipose differen tiation by RA in 3T3-L1 cells. Moreover, there seems no causal relatio nship between the prevention of adipose differentiation by RA and the up-regulation of RAR gamma 2 gene expression by RA in 3T3-L1 cells. We have shown the functional heterogeneity of RA action through differen t RARs in 3T3-L1 cells.