Vitamin A Supplementation and Retinol Metabolism in the Neonatal Period

新生儿期维生素A的补充和视黄醇的代谢

• 批准号: 9105886
• 负责人: A. CATHARINE ROSS
• 金额: $ 40.86万
• 依托单位: PENNSYLVANIA STATE UNIVERSITY, THE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-20 至 2020-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9105886
• 关键词: 5 year old; Address; Adult; Affect; Age; Age-Months; All-Trans-Retinol; Animal Model; Back; Child; Child Mortality; Chylomicrons; Clinical Trials; Development; Diet; Dietary Intervention; Dietary Supplementation; Dose; Drug or chemical Tissue Distribution; Esters; Exposure to; Extrahepatic; Female; Future; Goals; Grant; Growth and Development function; Health; Human; Immunity; Infant; Intake; Intestines; Kinetics; Knowledge; Learning; Life; Liver; Lung; Metabolism; Milk; Modeling; Mothers; Neonatal; Newborn Animals; Nurses; Oils; Oral; Organ; Placebo Control; Placebos; Plasma; Play; Policies; Process; Protocols documentation; Public Health; Randomized Controlled Trials; Rattus; Recycling; Research; Retinol Metabolism Pathway; Role; Route; Site; Small Intestines; Stomach; Supplementation; Testing; Time; Tissues; Tracer; Translating; Tretinoin; Vitamin A; Vitamin A Deficiency; World Health Organization; absorption; age group; base; body system; chylomicron remnant; cost; cost efficient; design; feeding; global health; improved; insight; interest; low income country; male; mathematical model; mortality; neonate; postnatal; public health relevance; trafficking; uptake

 DESCRIPTION (provided by applicant): Vitamin A (VA) is known to be essential for the postnatal growth and development of immature organ systems and establishment of immunity, yet VA metabolism in neonates is virtually unstudied. Currently, the World Health Organization (WHO) promotes VA supplementation of young children >6 months of age in low-income countries where VA deficiency is still a public health problem, as a means to reduce young child mortality and improve global health. However, VA supplementation of neonates (infants < 6 mo of age) is controversial and WHO has not established a policy for this age group. Our goal is to use a cost-efficient and well-validated animal model to learn, in depth, how VA, when provided either at non-supplemental or supplemental doses, is absorbed and trafficked throughout the body. We will use two different protocols, direct VA supplementation of neonates and indirect supplementation through addition of VA to the maternal diet, to test our central hypothesis, namely: Direct VA supplementation of neonates, through oral VA supplementation, and indirect VA supplementation, through increased maternal dietary VA, will be significantly, but differently, alter whole-body retinol kinetics in neonates. Moreover, we believe based on our preliminary studies that these routes of administration will differ. Our goal is to provide fundamental new knowledge on retinol absorption, trafficking, and tissue distribution in a neonatal rat model using a whole-body approach that is based on 3H-retinol kinetic analysis and mathematical modeling. Because our results from the previous grant period have suggested the importance of extrahepatic tissues in the clearance of newly absorbed VA carried in chylomicrons (CM), we will focus on CM VA metabolism and on its transport from the intestine and uptake by extrahepatic tissues as well as by the liver. We also have obtained preliminary evidence that retinoic acid (RA), the most active metabolite of retinol, may drive retinol into these extrahepati organs. Therefore, in aim 1.1 we will conduct a study using 3H-retinol tracer kinetics and mathematical modeling studies of neonates that have been supplemented directly with VA, given at a dose what resembles that which has been administered to young children, compared to an oil placebo. Both male and female neonates will be included in the design. Aim 1.2 will also address the importance of RA in determining whole-body VA kinetics in neonates. Aim 2 will address retinol kinetics in the neonate after indirect supplementation through addition of VA to the diet of the mother, whose milk VA concentration will be augmented. By conducting these two aims, we will gain fundamental new information that could inform future policies regarding VA supplementation in human neonates. Since VA supplementation is a practical, low-cost nutritional intervention, if positive results are obtained from our research they could be readily translated into clinical trials.

 描述（由适用提供）：已知维生素A（VA）对于未成熟器官系统的产后生长和发育至关重要，而新生儿的VA代谢几乎没有研究。目前，世界卫生组织（WHO）在低收入国家中促进了少少年儿童的VA补充，那里VA缺乏症仍然是一个公共卫生问题，作为降低幼儿死亡率并改善全球健康状况的一种手段。但是，补充新生儿（年龄<6 mo）的VA是有争议的，并且尚未建立该年龄段的政策。我们的目标是使用一种具有成本效益且良好的动物模型，深入学习，当以非育种或补充剂量提供时，VA如何吸收并在整个身体中吸收。 We will use two different protocols, direct VA supplementation of neonates and indirect supplementation through addition of VA to the maternal diet, to test our central hypothesis, namely: Direct VA supplementation of neonates, through oral VA supplementation, and indirect VA supplementation, through increased maternal dietary VA, will be significantly, but differently, alter whole-body retinol kinetics in neonates.此外，我们认为，基于我们的初步研究，这些行政途径会有所不同。我们的目标是使用新生大鼠模型中的视黄醇抽象，贩运和组织分布提供基本的新知识 一种基于3H-归因动力学分析和数学建模的全身方法。因为我们从上一定赠款期开始的结果表明，肝外组织的重要性在清除新近吸收的VA（CM）中，我们将重点关注CM VA代谢，以及从肠外肠外肠外组织以及肝脏以及肝脏以及肝脏的摄取。我们还获得了初步证据表明，视黄酸是视黄醇的代谢产物，可能会将视黄醇驱动到这些外膜外器官中。因此，在AIM 1.1中，我们将使用3H-归因醇示踪剂动力学和对直接补充VA补充的新生儿的数学建模研究进行研究，并以与油的安慰剂相比，以某种相似的类似于给幼儿的剂量。男性和女性新生儿都将包括在设计中。 AIM 1.2还将解决RA在确定新生儿全身VA动力学方面的重要性。 AIM 2通过将VA添加到母亲的饮食中，将在新生儿的新生儿中解决视黄醇动力学，其牛奶VA浓度将得到增强。通过实现这两个目标，我们将获得基本的新信息，这些信息可以为未来的人类新生儿补充提供信息。由于补充VA是一种实用的低成本营养干预，如果从我们的研究中获得积极的结果，则可以很容易地将其转化为临床试验。