Regulation of hepatic lecithin: retinol acyltransferase activity by retinoic acid

The activity of the hepatic enzyme lecithin: retinol acyltransferase (LRAT), thought to catalyze the esterification of retinol for storage, was previously shown to vary directly with the vitamin A (retinol) status of the rat [Randolph, R. K., and Ross, A. C. (1991) J. Biol. Chem. 266, 16453-16457]. The present studies were designed to determine whether liver LRAT activity is regulated in vivo by retinoic acid, a principal active metabolite of retinol. LRAT activity was negligible in the livers of vitamin A-deficient rats. Following treatment with a single 2-micrograms dose of retinoic acid, LRAT activity increased significantly while, following treatment with a single 20-micrograms dose, liver LRAT activity equalled that of vitamin A-sufficient adult rats. Retinoic acid was more effective than an equimolar quantity of retinol in restoring LRAT activity in the vitamin A-deficient rat liver. The increase in hepatic LRAT activity after administration of retinoic acid occurred rapidly, reaching a maximum within 12-16 h but declining again after 48-72 h. Studies were conducted in vivo to gain insight into the level of regulation of LRAT by retinoic acid. The increase in LRAT activity by retinoic acid in the vitamin A-deficient rat was blocked completely by both actinomycin D and cycloheximide. The ability of liver to esterify retinol in vivo was correlated with the in vitro activity of LRAT after retinoic acid induction. We conclude that retinoic acid, an important end product of retinol metabolism, regulates a key aspect of hepatic retinol metabolism through its regulatory activity on liver LRAT.