Regulation of hepatic vitamin A storage in a rat model of controlled vitamin A status during aging

It is currently unknown whether the capacity of the liver to esterify and s tore vitamin A (VA) changes as a function of long-term VA intake or age. Th e objective of this study was to investigate whether age and/or VA status a re factors for the hepatic expression of cellular retinol-binding protein ( CRBP), the esterification of retinol by lecithin:retinol acyltransferase (L RAT) and the accumulation of VA and lipids in liver, Two factors, VA intake and age, were studied in a 3 x 3 design. Diets denoted as VA-marginal, con trol and supplemented contained 0.35, 4 and 25 mg retinol equivalents/kg di et, respectively; male Lewis rats were fed these diets from weaning until t he ages of 2-3 mo (young), 8-10 mo (middle-aged) and 18-20 mo told) (n = 6/ group, Liver CRBP mRNA differed two-way ANOVA) with dietary VA (P < 0.0001) and age (P < 0.05), Hepatic LRAT activity increased with dietary VA (P < 0 .0001). Age was not a factor (P = 0.47) although there was an interaction o f age and dietary VA (P < 0.0001). Hepatic LRAT activity was correlated (r = 0.633, P < 0.0001) with plasma retinol at physiologic concentrations. In VA-supplemented rats of all ages, the plasma molar ratio of total retinol:r etinol-binding protein (RBP) exceeded 1, and liver VA and total lipid conce ntrations were elevated. However, tests of liver function had previously be en shown to be within normal values. Thus, the capacity of the liver for re tinol esterification by LRAT was not diminished by age or the accumulation of VA and other lipids. We conclude the following: 1) hepatic LRAT activity is regulated across a broad, physiologic range of dietary VA; 2) LRAT acti vity is regulated throughout life; and 3) the capacity for hepatic VA stora ge is high throughout life.