RETINOIDS ARE POSITIVE EFFECTORS OF ADIPOSE CELL-DIFFERENTIATION

Retinoids, especially all-trans retinoic acid (t-RA), have been report ed in the last decade to inhibit the differentiation of preadipose cel ls. In those studies, however, the concentrations of t-RA were supraph ysiological (0.1-10 mu M range). In contrast we show that, when presen t at concentrations below or close to the K-d 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 subtyp e, these positive effects on adipose differentiation involve in partic ular the RAR alpha subtype, and have been observed in Ob17 cells expos ed to serum-supplemented or serum-free medium,. and in rat preadipocyt es exposed to serum-free medium. Among the two classes of retinoid aci d receptors (RARs) and retinoid X receptors (RXRs), RAR alpha, RAR gam ma, RXR alpha and RXR beta mRNAs could be detected in growing adipobla sts and were found to be increased in committed preadipocytes and diff erentiated cells upon retinoid treatment. Like other adipogenic hormon es, retinoids were only effective in the terminal differentiation proc ess leading from preadipocytes to adipocytes.