Neonatal Nutrition and the Genetics of Human Lactation

描述(由申请人提供)： 哺乳是一种生理状态，在这种状态下，母亲的营养状况会对孩子的生长发育产生深远的影响。大量文献表明，新生儿摄入充足的二十二碳六烯酸(DHA)对大脑的最佳成熟至关重要。然而，新生儿将膳食必需脂肪酸前体转化为DHA的能力有限；因此，婴儿可能严重依赖母乳来获得充足的DHA供应。然而，哺乳期的乳房不能合成DHA，因此它必须来自饮食来源。餐后乳糜管在将膳食中的DHA输送到哺乳乳房中起着核心作用。因此，改变乳糜管代谢的母体基因多态也可能影响DHA向母乳中运输的效率，并最终可能成为决定婴儿是否获得足够的DHA摄入量的主要决定因素。因此，我们提出以下假设：1)在餐后状态下，餐后乳胶微粒血症的大小和持续时间将直接与膳食DHA向母乳的转运效率相关；2)调节乳糜管组装、血管内代谢或肝脏清除的基因多态性将直接影响膳食DHA向母乳的转运效率。为了验证这些假设，我们提出了两个特定的目标：1)在一组未选定的哺乳期妇女中检测餐后乳糜管代谢，并将DHA转运与DHA进入母乳的转运联系起来；2)在匹配的等位基因携带者和对照组中，检查载脂蛋白A-IV-2等位基因对餐后乳糜管代谢和DHA进入母乳的转运的特定影响。我们预计，从这项初步研究中获得的数据可以为将来研究调节母乳营养含量的其他基因多态奠定基础。这一知识最终可能使识别需要特定脂肪酸或维生素补充以确保婴儿最佳营养的妇女成为可能。

DESCRIPTION (provided by applicant): Lactation is a physiologic state in which the nutritional status of the mother can have a profound impact on the growth and development of the child. A large body of literature suggests that adequate neonatal intake of docosahexaenoic acid (DHA) is critical for optimal brain maturation. However, the neonate has a limited capacity to convert dietary essential fatty acid precursors into DHA; thus, the infant may be critically dependent upon mother's milk for an adequate supply of DHA. However, the lactating breast cannot synthesize DHA; thus it must derive from dietary sources. Post-prandial chylomicrons play a central role in the transport of dietary DHA to the lactating breast. Therefore, maternal genetic polymorphisms that alter chylomicron metabolism could also affect the efficiency of DHA transport into breast milk, and could ultimately be a major determinant as to whether an infant receives an adequate DHA intake. We therefore propose the following hypotheses: 1) In the post prandial state the magnitude and duration of post prandial chylomicronemia will directly correlate with the transport efficiency of dietary DHA into breast milk; 2) Genetic polymorphisms that modulate chylomicron assembly, intravascular metabolism, or hepatic clearance will have a direct impact on the transport efficiency of dietary DHA into breast milk. To examine these hypotheses we propose two specific aims: 1) Examine postprandial chylomicron metabolism in an unselected cohort of lactating women and correlate chylomicron DHA transport with the transport of DHA into breast milk; 2) Examine the specific impact of the apo A-IV-2 allele, which is known to delay chylomicron clearance, on postprandial chylomicron metabolism and the transport of DHA into breast milk in matched cohorts of allele carriers and controls. We anticipate that data forthcoming from this pilot study could establish the foundation for future studies of other genetic polymorphisms that regulate the nutritional content of breast milk. This knowledge could eventually enable the identification of women who require specific fatty acid or vitamin supplementation to assure optimal infant nutrition.