Humans obtain carotenoids in the diet from fruits and vegetables. The role of carotenoids as antioxidants has been the focus of our work on lipoprotein oxidation. While it is clear that lipoproteins are the main vehicles for transport of carotenoids, little is known about mechanisms of intestinal absorption of carotenoids. We now seek to define the mechanism(s) of intestinal absorption of carotenoids and their distribution into blood cells. We focus on the interaction of carotenoids and the human monocyte/macrophage since this interaction may play a role in the development of atherosclerosis.
Specific aims are: 1. Mechanisms of intestinal absorption of carotenoids and their incorporation into chylomicrons in CACO-2 cells in culture. We will test the hypothesis that other fat-soluble nutrients inhibit the incorporation of beta-carotene into chylomicrons. We will test the hypothesis that SRB1, CD-36, FAT, and other putative lipid transporters mediate the uptake of beta-carotene into the cell. We will test the hypothesis the increasing the expression of beta-carotene 15,15' dioxygenase increases the total flux of beta-carotene through the cell. 2. Intestinal absorption of beta-carotene in humans. We will use stable isotope methodology to study the mechanisms of the intestinal absorption of beta- carotene in humans. The general question under investigation is whether there are common mechanisms for the absorption of various fat-soluble dietary nutrients. We will test the hypothesis that the efficiency of intestinal absorption of cholesterol is positively correlated with the efficiency of the intestinal absorption of beta-carotene. We will test the hypothesis that beta-carotene is converted to vitamin A solely in the intestine. We will quantify the conversion of beta-carotene to vitamin A to test the hypothesis that increased absorption of beta-carotene is associated with increased conversion to vitamin A. 3. Modulation of macrophage function by dietary carotenoids. We will use the U937 cell line as well as human peripheral blood monocyte- macrophages to examine the partitioning of carotenoids into blood-borne cells and the effects of carotenoid enrichment on monocyte-macrophage function. We will test the hypothesis that plasma carotenoids partition into various blood cells as well as into plasma lipoproteins. We will test the hypothesis that carotenoid enrichment alters monocyte-macrophage phenotype, either enhancing or inhibiting potentially pro-atherosclerotic aspects of cell function including response to chemotactic stimuli, adhesion to endothelial cells, differentiation into macrophages, ability to oxidize LDL, and ability to form foam cells.
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