Regulation of hepatic lecithin:retinol acyltransferase activity by retinoic acid receptor-selective retinoids

Academic Article

Abstract

  • 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) alltrans-UAB8 and the RAR-α-selective retinoid Am580 also strongly induced LRAT activity. In contrast, neither RXR-selective agonists nor retinoids having a retro structure were active. For retinoids with significant RAR-α binding activity there was a strong direct correlation between receptor binding in vitro and the ability to induce hepatic LRAT activity in 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.
  • Digital Object Identifier (doi)

    Author List

  • Shimada T; Ross AC; Muccio DD; Brouillette WJ; Shealy YF
  • Start Page

  • 220
  • End Page

  • 227
  • Volume

  • 344
  • Issue

  • 1