Investigation into the mechanisms by which maternal diet impacts on offspring health the role of programmed changes in the leptin axis

一个人的饮食在人生的任何阶段都有重要的健康问题。然而，有证据表明，孕妇和哺乳期妇女的饮食特别重要，因为它对其婴儿的健康有重大的长期影响。研究表明，出生体重低的人不仅不太可能存活下来，而且成年后患肥胖症的风险也大大增加。相比之下，母乳喂养的婴儿比奶粉喂养的婴儿生长更慢，更不可能在以后的生活中变得肥胖。早期生长和后来肥胖之间关系的根本原因尚不清楚，但我们认为，妇女在怀孕和哺乳期间的饮食质量至关重要。我们已经在啮齿动物模型中表明，如果怀孕的动物在怀孕期间蛋白质太少，它们的婴儿在出生时很小，成年后更有可能肥胖。我们认为这是因为这些动物吃得更多，运动更少。在我们的啮齿动物模型中，动物在哺乳期生长缓慢，因为它们的母亲吃的是低蛋白质的食物，即使给动物提供高度可口的食物，动物也不会变胖。我们已经在大脑中发现了一个重要的基因，该基因在动物体内的表达水平较高，对肥胖具有抵抗力。我们认为这使这些动物对一种蛋白质瘦素更有反应。这种蛋白质由脂肪细胞产生，并向大脑发出抑制食欲和增加能量消耗的信号。在这项提案中，我们将通过给肥胖倾向和肥胖抵抗的动物注射瘦素，然后测量它们的食物摄入量和能量消耗来测试这一想法。我们还将进一步研究这些动物的大脑，以确定在不同水平上表达的其他基因。我们将研究动物大脑中的DNA，以确定为什么特定的基因没有正确表达。了解这些过程将使我们能够识别高危个体，并制定干预战略，以改善孕妇和哺乳期妇女及其后代的健康。

The diet of an individual has important health issues at any stage of life. However there is evidence to suggest that the diet of pregnant and lactating women is particularly important as it has major long-term implications on the health of their babies. It has been shown that individuals with a low birth weight are not only less likely to survive delivery but are also at substantially increased risk of developing obesity as adults. In contrast breast-fed infants, who are known to grow more slowly than bottle-fed infants, are less likely to become obese later in life. The underlying causes of the relationship between early growth and later obesity are not known but we believe that the quality of the diet of women during pregnancy and during breast-feeding is critically important. We have shown in a rodent model that if pregnant animals have too little protein during pregnancy their babies are small at birth and are more likely to become obese in adulthood. We think this is because these animals eat more and exercise less. In contrast in our rodent model where animals grow slowly during lactation because their mothers are eating a diet low in protein, the animals do not get fat even when offered a highly palatable diet. We have identified an important gene in the brain that is expressed at higher levels in animals that are resistant to obesity. We think this makes these animals more responsive to a protein leptin. This protein is produced by fat cells and signals to the brain to suppress appetite and to increase energy expenditure. In this proposal we will test this idea by giving obesity-prone and obesity-resistant animals leptin and then measuring their food intake and energy expenditure. We will also study the brains of these animals further to identify other genes that are expressed at different levels. We will study the DNA from the brains of our animals to determine why particular genes are not expressed properly. Understanding these processes will enable us to both identify at risk individuals and to develop intervention strategies to improve the health of both pregnant and breast-feeding women and their offspring.