Retinoid X receptor (RXRα) gene expression is regulated by fatty acids and dexamethasone in hepatic cells

This work describes the molecular mechanism of fatty acid and hormonal modulation of retinoid X receptor (RXRα) in rat liver. We examined the effects of different fatty acids (myristic-, stearic-, linolenic-, oleic-, arachidonic- and tetradecylthioacetic acid (TTA)) and the synthetic glucocorticoid dexamethasone on RXRα mRNA and protein steady-state levels in hepatoma cells and cultured hepatocytes. Fatty acids induced the RXRα gene expression where TTA showed the most inductive effect (three-fold induction). Dexamethasone alone resulted in a stronger induction (up to seven-fold in hepatocytes), and in combination with fatty acids, an additive or synergistic effect was observed. The RXRα protein level in cultured hepatocytes showed a similar pattern of regulation, with a slight inductive effect of fatty acids and an additive or synergistic effect was observed in combination with dexamethasone. Our results indicate that the RXRα gene expression is under distinct regulation by fatty acids and dexamethasone acid which strongly suggests a coupling with the lipid metabolizing system and the retinoid signaling pathway.