Dietary Fat and Amino Acid Interactions in Normal Development

在出生前，生长发育所需的营养物质是通过胎盘从母体循环中转移来满足的。主要的能量来源是葡萄糖和氨基酸，它们提供了约85%的胎儿能量供应。胎盘脂肪酸转移是低的，约占胎儿能量供应的11%在足月妊娠。出生后，牛奶饮食有很大的不同，提供大约50%的能量是脂肪，蛋白质更少。几十年前的研究表明，胎儿肝脏中脂肪酸氧化酶的活性较低，出生后会增加，并在母乳喂养期间保持较高的活性。当时，激素被认为是产后肝脏变化的重要因素；基因表达调控的重要性，以及必需的n-3脂肪酸在代谢调控中的重要性在很大程度上是未知的。近年来，关于n-3脂肪酸的知识急剧增加，其中包括二十二碳六烯酸（DHA）和二十碳五烯酸在调节成人肝脏脂肪酸合成和葡萄糖氧化中的作用。我们的兴趣是DHA在肝脏代谢发育中的作用，特别是处理高脂肪牛奶饮食和有效利用蛋白质。我们最近的研究提供了令人信服的证据，表明孕期和哺乳期饮食中的脂肪酸决定了通过胎盘转移并在乳汁中分泌的脂肪酸，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的表达变化有关，还与氨基酸代谢的基因表达变化有关。这项研究将结合我们在营养代谢和质谱方面的技能，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，并代表葡萄糖重定向到戊糖磷酸途径，这对于DNA和RNA所需的核糖的合成至关重要，而非必需氨基酸丝氨酸和甘氨酸则在甲基转移和抗氧化剂谷胱甘肽中起作用。这些新研究将对DHA在正常肝脏发育中的重要性以及脂肪酸、葡萄糖和氨基代谢的整合产生新的认识。

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.