The goal of the proposed research is to obtain basic information on how maternal diet and nutrition affect the composition of milk and the health of the neonate. The proposal focuses on the delivery of vitamin A (retinol) from mother to young during pregnancy and lactation. Specific goals 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 fed a basal vitamin A diet changes milk vitamin A content and whether acute supplementation will significantly expand the weanling's liver stores of vitamin A; 3) to explore whether expanded liver and body stores of retinol have functional effects on growth or 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 its transport protein retinol-binding protein (RBP), as well as transthyretin (TTR) in serum of animals from pre-pregnancy through lactation. We also plan to investigate possible differences in the molecular form of the vitamin A transport complex in the adult and fetal animal. In all studies, semisynthetic diets will be fed to control the content of vitamin A, fat and protein, and food consumption will be monitored. 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 gestational development will be explored using gel permeation chromatography, electrophoresis, and immunoassays. Because vitamin A is essential for reproduction, growth, and normal differentiation of epithelia, it is essential to understand the effects of maternal nutrition and the mechanisms that regulate the transport of this nutrient from mother to young during gestation and lactation.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
2R01HD016484-04
Application #
3313693
Study Section
Nutrition Study Section (NTN)
Project Start
1982-04-01
Project End
1988-06-30
Budget Start
1985-07-01
Budget End
1986-06-30
Support Year
4
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Allegheny University of Health Sciences
Department
Type
Schools of Medicine
DUNS #
City
Philadelphia
State
PA
Country
United States
Zip Code
19129
Ross, A C (1993) Cellular metabolism and activation of retinoids: roles of cellular retinoid-binding proteins. FASEB J 7:317-27
Randolph, R K; Winkler, K E; Ross, A C (1991) Fatty acyl CoA-dependent and -independent retinol esterification by rat liver and lactating mammary gland microsomes. Arch Biochem Biophys 288:500-8
Randolph, R K; Ross, A C (1991) Vitamin A status regulates hepatic lecithin: retinol acyltransferase activity in rats. J Biol Chem 266:16453-7
Randolph, R K; Ross, A C (1991) Regulation of retinol uptake and esterification in MCF-7 and HepG2 cells by exogenous fatty acids. J Lipid Res 32:809-20
Ross, A C (1990) Separation of fatty acid esters of retinol by high-performance liquid chromatography. Methods Enzymol 189:81-4
Pasatiempo, A M; Ross, A C (1990) Effects of food or nutrient restriction on milk vitamin A transfer and neonatal vitamin A stores in the rat. Br J Nutr 63:351-62
Ross, A C (1990) Measurement of acyl coenzyme A-dependent esterification of retinol. Methods Enzymol 189:442-5
Pasatiempo, A M; Bowman, T A; Taylor, C E et al. (1989) Vitamin A depletion and repletion: effects on antibody response to the capsular polysaccharide of Streptococcus pneumoniae, type III (SSS-III). Am J Clin Nutr 49:501-10
McCloskey, H M; Glick, J M; Ross, A C et al. (1988) Effect of fatty acid supplementation on cholesterol and retinol esterification in J774 macrophages. Biochim Biophys Acta 963:456-67
Marinari, L; Lenich, C M; Ross, A C (1987) Production and secretion of retinol-binding protein by a human hepatoma cell line, HepG2. J Lipid Res 28:941-8

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