The overall objective of the first project is to understand the delivery of vitamin A (retinol) from mother to young during pregnancy and lactation.
The specific aims are 1) to understand how diets that differ widely in fat and/or protein content affect retinol transport in milk and neonatal stores of vitamin A; 2) to understand how acute supplementation with retinyl acetate or Beta-carotene to pregnant or nursing rats changes milk retinyl ester content and whether acute supplementation will significantly expand the weanling's vitamin A stores; 3) to explore whether such expanded stores of retinol have functional effects on growth and the ability of the neonate to respond immunologically to an antigen challenge; and 4) to obtain a comprehensive profile of the levels of retinol and retinol-binding protein (RBP), as well as transthyretin (TTR), in serum of animals from before pregnancy through lactation. We also plan to investigate possible changes in the molecular form of the vitamin A transport complex in the pregnant and lactating animal. In all studies, semisynthetic diets will be fed to control the content of vitamin A, dietary fat and protein. Sensitive assays will allow measurement of retinol concentrations, retinyl ester patterns, and fatty acid profiles in milk samples collected from day 1 to near the end of lactation. Immunoassays will be used to measure specifically the levels of RBP and TTR in serum of dams or pups. Possible changes in the size and characteristics of the retinol transport complex during pregnancy will be explored using gel permeation chromatography by HPLC, electrophoresis, and immunoassays. The second project explores hepatic lipid metabolism, namely the synthesis and storage of retinyl and cholesteryl esters. Here, the goals are 1) to understand the assimilation of chylomicron lipids by liver cells, using isolated hepatoma or primary rat liver cells; 2) to explore the regulation of RBP secretion from normal and transformed liver cells; and 3) to study regulation of retinol and cholesterol acyltransferases in vitro. The long range objectives of these studies are to define and compare some of the basic mechanisms of uptake, esterification, and intracellular storage of dietary vitamin A and cholesteryl ester by the liver.
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