Postprandial Vitamin A

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DESCRIPTION (provided by applicant): Dietary vitamin A is absorbed in the intestine where it is converted to retinyl ester. This retinyl ester is packaged along with other dietary lipids into nascent chylomicrons and secreted into the lymphatic system. Upon entering the general circulation the chyiomicrons undergo metabolism that gives dse to chylomicron remnants that are cleared from the circulation by liver and other tissues. Approximately 66-75% of chylomicron remnant retinyl ester is taken up by the liver where it is either resecreted into the circulation as retinol bound to retinol-binding protein (RBP) or stored in hepatic stellate cells. The remaining postprandial vitamin A is cleared by extrahepatic tissues. At present, there is only very limited understanding of the biochemistry that underlies the uptake and processing of postprandial vitamin A, either by the liver or by other tissues. Our studies will provide new biochemical understanding of these processes. We are proposing to identify factors and to investigate mechanisms responsible for the uptake and processing of postprandial vitamin A within the liver and in extrahepatic tissues, especially focusing on heart and mammary tissue. All of our studies will be carried out in knockout and transgenic mice. In Aim 1, we propose to investigate how chylomicron remnant retinyl ester is taken up by hepatocytes and how the newly absorbed vitamin A is transferred from hepatocytes to hepatic stellate cells for storage. We will investigate the roles that RBP and cellular retinol-binding protein, type I (CRBPI) have in this process. Uptake of postprandial vitamin A into the heart will be examined in Aim 2. Unlike the liver, the heart does not store vitamin A. However, the heart has a relatively high need for retinoic acid for maintaining cellular health. In Aim 2, we will examine the roles that RBP and cellular retinol-binding protein, type III (CRBPIII) have in facilitating cardiac retinoic acid synthesis from postprandial vitamin A and in retinol resecretion from the heart. In Aim 3 we plan to explore how postprandial vitamin A is taken up and processed by mammary tissue for incorporation into milk. Our preliminary data indicates that postprandial vitamin A is an important source of the vitamin A present in milk. Here, we will focus on the roles that RBP, CRBPI, CRBPIII and lipoprotein lipase have in facilitating postprandial vitamin A incorporation into milk.