Vitamin A deficiency during the perinatal period induces changes in vitamin A metabolism in the offspring. The regulation of intestinal vitamin A metabolism via ISX occurs only in male rats severely vitamin A-deficient.

PURPOSE: 1) To test the hypothesis of the existence of a perinatal vitamin A (VA) programming of VA metabolism and to better understand the intestinal regulation of VA metabolism. METHODS: Offspring from rats reared on a control (C) or a VA-deficient (D) diet from 6 weeks before mating until offspring weaning, i.e., 7 weeks after mating, were themselves reared on a C or D diet for 19 weeks, resulting in the following groups: C-C (parents fed C-offspring fed C), D-C, C-D and D-D. VA concentrations were measured in plasma and liver. ß-Carotene bioavailability and its intestinal conversion rate to VA, as well as vitamin D and E bioavailability, were assessed after gavages with these vitamins. Expression of genes involved in VA metabolism and transport was measured in intestine and liver. RESULTS: C-D and D-D had no detectable retinyl esters in their liver. Retinolemia, hepatic retinol concentrations and postprandial plasma retinol response to ß-carotene gavage were higher in D-C than in C-C. Intestinal expression of Isx was abolished in C-D and D-D and this was concomitant with a higher expression of Bco1, Scarb1, Cd36 and Lrat in males receiving a D diet as compared to those receiving a C diet. ß-Carotene, vitamin D and E bio-availabilities were lower in offspring receiving a D diet as compared to those receiving a C diet. CONCLUSION: A VA-deficient diet during the perinatal period modifies the metabolism of this vitamin in the offspring. Isx-mediated regulation of Bco1 and Scarb1 expression exists only in males severely deficient in this vitamin. Severe VA deficiency impairs ß-carotene and vitamin D and E bioavailability.

ß-Carotene Bioavailability and Conversion Efficiency Are Significantly Affected by Sex in Rats: First Observation Suggesting a Possible Hormetic Regulation of Vitamin A Metabolism in Female Rats.

SCOPE: To study the effect of variation in dietary vitamin A (VA) content on its hepatic and intestinal metabolism. METHODS AND RESULTS: Adult female and male rats are fed with diets containing 400, 2300, or 9858 IU kg-1 VA for 31-33 weeks. VA concentrations are measured in plasma and liver. Bioavailability and intestinal conversion efficiency of ß-carotene to VA are assessed by measuring postprandial plasma ß-carotene and retinyl palmitate concentrations after force-feeding rats with ß-carotene. Expression of genes involved in VA metabolism, together with concentrations of RBP4, BCO1, and SR-BI proteins, are measured in the intestine and liver of female rats. Plasma retinol concentrations are lower and hepatic free retinol concentrations are higher in females than in males. There is no effect of dietary VA content on ß-carotene bioavailability and its conversion efficiency, but bioavailability is higher and conversion efficiency is lower in females than in males. The expression of most genes exhibited a U-shaped dose response curve depending on VA intake. CONCLUSIONS: ß-Carotene bioavailability and conversion efficiency to VA are affected by the sex of rats. Results of gene expression suggest a hormetic regulation of VA metabolism in female rats.