Retinoids are positive effectors of adipose cell differentiation

Retinoids, especially all-trans retinoic acid (t-RA), have been reported in the last decade to inhibit the differentiation of preadipose cells. In those studies, however, the concentrations of t-RA were supraphysiological (0.1-10 microM range). In contrast we show that, when present at concentrations below or close to the Kd values of retinoic acid receptors, retinoids behave as potent adipogenic hormones (1 pM to 10 nM range). As shown by the use of specific ligands for each RAR subtype, these positive effects on adipose differentiation involve in particular the RAR alpha subtype, and have been observed in Ob17 cells exposed to serum-supplemented or serum-free medium, and in rat preadipocytes exposed to serum-free medium. Among the two classes of retinoid acid receptors (RARs) and retinoid X receptors (RXRs), RAR alpha, RAR gamma, RXR alpha and RXR beta mRNAs could be detected in growing adipoblasts and were found to be increased in committed preadipocytes and differentiated cells upon retinoid treatment. Like other adipogenic hormones, retinoids were only effective in the terminal differentiation process leading from preadipocytes to adipocytes.