Dietary Fat and Amino Acid Interactions in Normal Development

在出生之前，生长和发育的营养需求是通过母体循环中的胎盘营养转移来满足的。主要的能量来源是葡萄糖和氨基酸，它们提供了大约85%的胎儿能量供应。胎盘脂肪酸转移量很低，约占足月妊娠胎儿能量供应的11%。出生后，牛奶的饮食有了很大的不同，提供了大约50%的脂肪能量，蛋白质含量较低。几十年前的研究表明，脂肪酸氧化酶在胎儿肝脏中活性较低，出生后活性增加，并在哺乳期间保持较高活性。当时，激素被认为在出生后肝脏的变化中很重要；基因表达的调节以及必需的n-3脂肪酸在代谢调节中的重要性在很大程度上是未知的。近年来，对n-3脂肪酸的认识急剧增加，其中包括二十二碳六烯酸(DHA)和二十碳五烯酸在成人肝脏中调节脂肪酸合成和葡萄糖氧化的作用。我们感兴趣的是DHA在肝脏新陈代谢发展中的作用，特别是在处理高脂肪牛奶饮食和有效利用蛋白质方面。我们最近的研究提供了令人信服的证据，即怀孕和哺乳期饮食中的脂肪酸决定了通过胎盘转移并分泌到牛奶中的脂肪酸，以及发育中的后代肝脏中的DHA。反过来，这不仅与脂肪酸和葡萄糖基因表达的变化有关，也与氨基酸代谢的变化有关。这项研究将结合我们在营养代谢和质谱学方面的技术，表明DHA在发育中的肝脏中基因和蛋白质表达的变化是有意义的，代表着葡萄糖重定向到戊糖磷酸途径，这是合成DNA和RNA所需核糖的关键，以及非必需氨基酸丝氨酸和甘氨酸，它们在甲基转移和抗氧化剂谷胱甘肽中起作用。这些新的研究将产生关于DHA在正常肝脏发育中的重要性的新知识，还将整合脂肪酸、葡萄糖和氨基酸代谢。

Before birth, nutrient needs for growth and development are met by placental nutrient transfer from the maternal circulation. The major energy sources are glucose and amino acids, which provide about 85% of the fetal energy supply. Placental fatty acid transfer is low, representing about 11% of the fetal energy supply at term gestation. After birth, the milk diet differs dramatically, providing about 50% energy as fat, with lower protein. Studies several decades ago showed the activity of enzymes of fatty acid oxidation are low in fetal liver, then increase after birth and remain high during milk feeding. At that time, hormones were considered important in the postnatal changes in liver; the importance of regulation of gene expression, and of the essential n-3 fatty acids in metabolic regulation was largely unknown. Knowledge on the n-3 fatty acids has increased dramatically in recent years, and this includes the role of docosahexaenoic acid (DHA) and eicosapentaenoic acid in regulating fatty acid synthesis and glucose oxidation in the adult liver. Our interest is the role of DHA in metabolic development in the liver, specifically the handling of the high fat milk diet and efficient use of protein. Recent studies by us provide compelling evidence that fatty acids in the diet in pregnancy and lactation determine the fatty acids transferred across the placenta and secreted in milk, and DHA in the developing offspring liver. This in turn, is associated with changes in expression of genes not only of fatty acid and glucose, but also amino acid metabolism. This research will unify our skills in nutrient metabolism and mass spectrometry to show that changes in gene and protein expression in the developing liver by DHA are meaningful and represent redirection of glucose to the pentose phosphate pathway, which is critical for synthesis of ribose needed for DNA and RNA, and non-essential amino acids serine and glycine, which function in methyl transfer and the antioxidant glutathione. These novel studies will generate new knowledge on the importance of DHA in normal liver development, also integrating fatty acid, glucose and amino metabolism.