Postprandial Vitamin A

描述(申请人提供)：食物中的维生素A在肠道中被吸收，在那里它被转化为视黄酸酯。这种视黄酸酯与其他饮食脂肪一起包装成新生的乳糜粒，并分泌到淋巴系统。一旦进入一般循环，乳糜体就会进行代谢，使乳糜体残留物被肝脏和其他组织从循环中清除。大约66-75%的残余乳胶体视黄酸酯被肝脏摄取，在那里它要么作为视黄醇结合蛋白(RBP)被切除进入循环，要么储存在肝星状细胞中。餐后剩余的维生素A被肝外组织清除。目前，无论是肝脏还是其他组织，对餐后维生素A摄取和加工的生物化学了解非常有限。我们的研究将提供对这些过程的新的生化理解。我们建议找出导致肝脏和肝外组织摄取和处理餐后维生素A的因素，并研究其机制，特别是心脏和乳腺组织。我们的所有研究都将在基因敲除和转基因小鼠身上进行。在目标1中，我们计划研究残留的乳胶体视黄酸酯是如何被肝细胞摄取的，以及新吸收的维生素A是如何从肝细胞转移到肝星状细胞进行储存的。我们将研究RBP和细胞视黄醇结合蛋白I型(CRBPI)在这一过程中所起的作用。Aim 2将检查餐后维生素A进入心脏的情况。与肝脏不同，心脏不储存维生素A。然而，心脏对维甲酸的需求相对较高，以维持细胞健康。在目标2中，我们将研究RBP和细胞视黄醇结合蛋白III型(CRBPIII)在促进餐后维生素A合成心脏维甲酸和从心脏清除视黄醇方面所起的作用。在目标3中，我们计划探索餐后维生素A是如何被乳房组织吸收并加工成牛奶的。我们的初步数据表明，餐后维生素A是牛奶中维生素A的重要来源。在这里，我们将重点介绍RBP、CRBPI、CRBPIII和脂蛋白脂肪酶在促进餐后维生素A进入牛奶中的作用。

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.