Postprandial Vitamin A

描述（由申请人提供）：膳食维生素A在肠道中被吸收，在肠道中转化为视黄酯。这种视黄酯与其他膳食脂质一起沿着包装成新生乳糜微粒并分泌到淋巴系统中。乳糜微粒进入全身循环后，经过代谢，将dse转化为乳糜微粒残留物，这些残留物被肝脏和其他组织从循环中清除。大约66-75%的乳糜微粒残余视黄酯被肝脏吸收，在肝脏中，视黄酯作为与视黄醇结合蛋白（RBP）结合的视黄醇重新分泌到循环中，或储存在肝星状细胞中。剩余的餐后维生素A由肝外组织清除。目前，对肝脏或其他组织摄取和加工餐后维生素A的生物化学的了解非常有限。我们的研究将为这些过程提供新的生物化学理解。我们建议确定因素，并调查机制，负责摄取和加工餐后维生素A的肝脏和肝外组织，特别是心脏和乳腺组织。我们所有的研究都将在基因敲除和转基因小鼠中进行。在目的1中，我们建议研究乳糜微粒残余视黄酯是如何被肝细胞吸收的，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）在这一过程中的作用。将在目标2中检查心脏对餐后维生素A的摄取。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。在目的2中，我们将研究RBP和细胞视黄醇结合蛋白III型（CRBPIII）在促进心脏从餐后维生素A合成维甲酸和从心脏中提取视黄醇中的作用。在目标3中，我们计划探索餐后维生素A是如何被乳腺组织吸收和加工以掺入乳汁的。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掺入牛奶中的作用。

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.