Regulation of Hepatic Lecithin:Retinol Acyltransferase Activity by Retinoic Acid Receptor-Selective Retinoids

• Published in: Archives of biochemistry and biophysics 1997-08, Vol.344 (1), p.220-227
• Main Authors: Shimada, Takaki, Ross, A.Catharine, Muccio, Donald D., Brouillette, Wayne J., Shealy, Y.Fulmer
• Format: Article
• Language: English
• Subjects: Acyltransferases - metabolism; Animals; Female; lecithin:retinol acyltransferase; Microsomes, Liver - enzymology; Molecular Structure; Protein Binding; rat liver; Rats; Rats, Inbred Strains; Receptors, Retinoic Acid - metabolism; retinoic acid receptor; retinoid X receptor; Retinoid X Receptors; Retinoids - pharmacology; retinol esterification; Transcription Factors - metabolism; Tretinoin - pharmacology; Vitamin A - pharmacology; Vitamin A Deficiency - metabolism
• ISSN: 0003-9861; 1096-0384
• DOI: 10.1006/abbi.1997.0209

The microsomal enzyme LRAT esterifies retinol and has been implicated in the hepatic storage of vitamin A. Previously, we showed that hepatic LRAT activity is negligible during vitamin A deficiency and that all-trans-retinoic acid (all-trans-RA) rapidly induces the activity of liver LRAT in retinoid-deficient rats. In the present studies, we have examined the ability of natural and synthetic retinoids to induce liver LRAT activity in retinoid-deficient rats. The natural retinoids retinol, all-trans-RA (100 μg), 9-cis-RA, or equal molar amounts of other retinoids were injected ip and LRAT specific activity was measured in liver homogenates 17–18 h later. In retinoid-deficient rats, liver LRAT activity was extremely low [0.13 ± 0.03 pmol retinyl ester (RE)/min/mg liver protein, mean ± SE]. The natural retinoids retinol and all-trans-RA strongly induced LRAT activity (12.71 ± 1.09 and 13.10 ± 1.55 pmol RE/min/mg, respectively), whereas 9-cis-RA induced a lower level of LRAT activity (3.96 ± 1.88 pmol RE/min/mg,P< 0.001 vs all-trans-RA). The retinoic acid receptor (RAR)-selective analog (RAR pan-agonist) all-trans-UAB8 and the RAR-α-selective retinoid Am580 also strongly induced LRAT activity. In contrast, neither RXR-selective agonists nor retinoids having aretrostructure were active. For retinoids with significant RAR-α binding activity there was a strong direct correlation between receptor bindingin vitroand the ability to induce hepatic LRAT activityin vivo(r2= 0.920). These data implicate the RARs in the induction of hepatic LRAT and suggest a predominant role for RAR-α-active ligands.