Molecular mechanism of 9-cis-retinoic acid inhibition of adipogenesis in 3T3-L1 cells

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 α (RXRα) with peroxisome proliferator-activated receptor γ (PPARγ) 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 RXRα and PPARγ. These results suggest that 9-cis-RA could inhibit adipogenesis by activating RXR, and decrease both RXR and PPARγs levels in a RXR activation-independent manner.

► We examined the effects of 9-cis-RA on adipogenesis in mouse preadipocyte 3T3-L1.
► 9-cis-RA inhibited lipid accumulation in adipogenetically-induced 3T3-L1 cells.
► A RXR pan-antagonist suppressed the inhibitory effects of 9-cis-RA on adipogenesis.
► This antagonist had no effects on RXRα and PPARγ levels in 9-cis-RA-treated cells.
► 9-cis-RA-induced decrease in both RXRα and PPARγ was independent of RXR activation.