DIET, LIPID TRANSPORT AND METABOLISM

Project: Research project

Description

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.
StatusFinished
Effective start/end date7/1/856/30/90

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

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vitamin A
metabolism
lipids
diet
retinol-binding protein
hepatocytes
prealbumin
lactation
cholesteryl esters
immunoassays
milk
cholesterol acyltransferase
pregnancy
chylomicrons
liver
protein secretion
rats
diet study techniques
esterification
hepatoma