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The Journal of Lipid Research, Vol. 39, 744-754, April 1998
Copyright © 1998 by Lipid Research, Inc.

Original Article

Gene transcription of the retinoid X receptor (RXR) is regulated by fatty acids and hormones in rat hepatic cells

Correspondence to: Hilde Nebb Sørensen.

This work describes the molecular mechanisms of fatty acid and hormonal modulations of the retinoid X receptor (RXR) in rat liver cells. We examined the effects of different fatty acids (myristic, stearic, oleic, linolenic, and arachidonic acids, EPA, and the peroxisomal proliferator TTA) and several hormones (the glucocorticoid analogue dexamethasone, insulin, and retinoic acid) on the RXR mRNA and protein levels in rat hepatoma cells and cultured hepatocytes. The fatty acids induced the RXR gene expression resulting in up to 3-fold induction. Dexamethasone alone induced the mRNA level and, in combination with fatty acids, an additive or synergistic effect was observed. The dexamethasone-increased mRNA level was obliterated by insulin. The same pattern of regulation of the protein level was observed when determined in cultured hepatocytes, but the induced protein level showed a lower magnitude of stimulation than the mRNA level. This could indicate a post-transcriptional modulation of the RXR gene expression. Time course studies showed a maximal induction of mRNA and protein levels after 18 h and 48 h, respectively.

Our results uniformly show that the RXR gene expression is under distinct regulation by fatty acids and hormones which suggests a coupling with the lipid metabolizing system and the hormonal signaling pathway.—Steineger, H. H., B. M. Arntsen, Ø. Spydevold, and H. N. Sørensen. Gene transcription of the retinoid X receptor (RXR) is regulated by fatty acids and hormones in rat hepatic cells. J. Lipid Res. 1998. 39: 744–754.

Supplementary key words: dexamethasone, insulin, mRNA level, protein level, regulation

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