INHIBITION OF 3T3 ADIPOGENESIS BY RETINOIC ACID IS NOT MEDIATED BY CYTOPLASMIC RETINOIC ACID-BINDING PROTEIN

Retinoic acid (RA) inhibits 3T3 adipogenesis in a dose-dependent and r eversible manner, but its mechanism of action remains unknown. 3T3-F44 2A cell variants obtained by mutagenesis with nitrosoguanidine and/or selection with high RA concentrations showed different resistance to R A cytotoxicity and underwent adipose conversion of various extents whe n they were cultured in adipogenic conditions. Commitment to adipose d ifferentiation was also inhibited by RA in these clones. Gel filtratio n chromatography showed the presence of a cytosolic RA-binding activit y in the parental cells but not in three of the variant clones isolate d. We demonstrate that cytoplasmic RA-binding activity is not essentia l far the inhibitory effects of the retinoid on 3T3 adipogenesis, or f or resistance to RA cytotoxicity. Other mechanisms should be involved to explain the inhibition of adipose differentiation by RA. (C) 1994 A cademic Press, Inc.