Retinoid X receptor (RXR alpha) 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 (RXR alpha) 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 RXR alpha mRNA and protein steady-state levels in hepatoma cells and cultured hepatocytes. Fatty acids induced the RXR alpha 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 RXR alpha 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 RXR alpha 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.