Natural and synthetic retinoids induce hepatic lecithin: Retinol acyltransferase (LRAT) activity in vitamin A-deficient rats

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 a//-frans-retinoic acid (ATRA) rapidly induces the activity of liver LRAT in vitamin A-deficient (A-) rats. In the present study, we have examined the ability of some natural and synthetic retinoids to induce liver LRAT activity in A- rats. ATRA (100 ng) or equal molar amounts of other retinoids were injected i.p. After 17-18 h, LRAT specific activity was measured. In A- rats, liver LRAT activity was extremely low [0.13±0.03 pmol retinyl ester (RE) /min/mg liver protein, mean ±SEMJ. The natural retinoids ATRA and retinol strongly induced LRAT activity (13.10+1.55 and 12.71± 1.09 pmol RE/min/mg, respectively). 9-c/s-RA also induced LRAT activity (3.96±1.88 pmol RE/min/mg) which was. however, significantly lower than after ATRA or retinol. The retinoic acid receptor (RAR)-selective analog a//-frans-UAB8 and the RAR-alphaselective retinoid, Am580, also induced LRAT activity. In contrast, neither the administration of the RXR-selective 9-c/s-UAB8 nor of retinoids with a retro structure induced LRAT activity. These data imply that the induction of LRAT is likely to be related to retinoid-RAR complex formation. (Supported by NIH DK-46869, CA24968, the Uehara Foundation and the Howard Heinz Endowment).