Retinoic acid (RA) signaling is mediated by specific nuclear hormone receptors. Here we examined the effects of 9-cis-RA on adipogenesis in mouse preadipocyte 3T3-L1 cells. 9-cis-RA inhibits the lipid accumulation of adipogenetically induced 3T3-L1 cells. The complex of retinoid X receptor alpha (RXR alpha) with peroxisome proliferator-activated receptor gamma (PPAR gamma) is a major transcription factor in the process of adipogenesis, and the levels of these molecules were decreased by 9-cis-RA treatment. A RXR pan-antagonist suppressed 9-cis-RA's inhibitory effects on adipogenesis, but not on the intracellular levels of both RXR alpha and PPAR gamma. These results suggest that 9-cis-RA could inhibit adipogenesis by activating RXR, and decrease both RXR and PPAR gamma s levels in a RXR activation-independent manner. (c) 2013 Elsevier Inc. All rights reserved.