Dietary lipids and regulation of gene expression: role of maternal nutrition

母体营养最近被认为在后代的正常生长和发育中起着关键作用。怀孕期间过量或不足的营养物质暴露会改变胎儿生长过程中器官的结构和功能，引起后代的代谢变化。膳食脂肪是正常生长发育所必需的。孕期和哺乳期脂肪的消耗影响必需脂肪酸通过胎盘和母乳的转移，为后代的正常生长、发育和代谢功能提供这些脂肪酸。两种必需脂肪酸是亚油酸和亚麻酸，它们分别属于ω -6 （n-6）和n-3类。这些脂肪酸是长链脂肪酸的前体，如花生四烯酸（n-6）、二十碳五烯酸和二十二碳六烯酸（n-3），每种脂肪酸都有不同的功能。n-6和n-3脂肪酸的最佳平衡对于维持整个身体的平衡是必不可少的。目前尚不清楚在怀孕和哺乳期间改变n-6和n-3脂肪酸的比例是否会影响后代的生长、发育和代谢/生理功能。我们以C57Bl/6小鼠为模型，研究母体膳食脂肪对子代代谢的影响。我们将改变怀孕C57Bl/6小鼠饮食中n-6/n-3脂肪酸的比例，研究其对后代代谢途径调控的影响，尤其是脂质和胆固醇代谢。我们还将研究母体饮食是否对后代血管的收缩和松弛有影响。最后，我们将研究母体饮食的影响是否可以被后代的饮食所逆转，以及母体饮食影响的机制。本研究的新颖之处在于，其结果将首次证实母体饲粮n-6/n-3脂肪酸比例对子代代谢和生理的重要性。许多高素质的年轻专业人员将在一个新的研究领域接受五年以上的培训，这将使他们能够在学术界、工业界或政府部门进一步发展事业。

Maternal nutrition has recently been suggested to play a critical role in the proper growth and development of offspring. Over- or under-exposure to nutrients during pregnancy can alter the structure and function of organs during fetal growth, inducing metabolic changes in the offspring. Dietary fats are essential for proper growth and development. The consumption of fats during pregnancy and lactation influence the transfer of essential fatty acids across the placenta and through breast milk, providing these fatty acids for proper growth, development and metabolic functions of the offspring. Two essential fatty acids are linoleic acid and linolenic acid, which belong to the omega-6 (n-6) and n-3 class respectively. These fatty acids are the precursors of the longer chain fatty acids, such as arachidonic acid (n-6), and eicosapentaenoic and docosahexaenoic acid (n-3), each of which are required for different functions. An optimum balance of n-6 and n-3 fatty acids is essential to maintain whole body homeostasis. It is not known if changing the ratios of n-6 and n-3 fatty acids during pregnancy and lactation affects growth, development and metabolic/physiological functions of the offspring. We have established the C57Bl/6 mouse as a model to study the effect of maternal dietary fats on offspring metabolism. We will vary the n-6/n-3 fatty acid ratios in the diets of pregnant C57Bl/6 mice to study the effect on the regulation of metabolic pathways of the offspring, especially the lipid and cholesterol metabolism. We will also study if maternal diet has an effect on the contraction and relaxation of blood vessels of the offspring. Finally, we will study if the effects of maternal diet can be reversed by the diet of the offspring, and also the mechanisms that are responsible for the effects of maternal diet. This research is novel as the findings will, for the first time, establish the importance of maternal dietary n-6/n-3 fatty acid ratios on the offspring metabolism and physiology. Many highly qualified young professionals will be trained over five years in a novel research area, which will enable them further careers in academia, industry or government.