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

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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.