Endocrine and metabolic changes in offspring due to maternal obesity

Over the last 20 years, childhood obesity rates have risen greatly, such that they now constitute an international epidemic of childhood obesity. It is now accepted that nutritional changes during fetal development can predispose individuals to obesity and metabolic disease in adult life, resetting the expression of genes involved in energy homeostasis and consequently altering metabolic function. Intrauterine over-nutrition also predisposes the foetus to obesity and metabolic dysfunction in adulthood, and this likely contributes to the burgeoning onset of childhood obesity. This thesis aimed to explore the endocrine and metabolic changes induced by maternal obesity in male offspring, and the beneficial effects of exercise intervention early in life.The first study used a litter size adjustment model after birth to explore the early changes in the fat mass and obesity associated (FTO) gene expression in the hypothalamus and liver, as well as other key regulators of energy homeostasis. In humans, single-nucleotide polymorphisms (SNPs) of FTO have been linked to increased risk of obesity and FTO is highly expressed in the hypothalamus. Maternal obesity significantly increased FTO mRNA expression in the hypothalamus and significantly decreased it in the liver at weaning. Early overexpression of hypothalamic FTO correlated with increased adiposity and later food intake of siblings exposed to high fat diet suggesting upregulation of FTO may contribute to subsequent hyperphagia in line with some human studies. No effect of maternal obesity was observed on FTO in adulthood. The second study assessed the long lasting effects of exercise intervention early in life in offspring of obese dams. Male offspring underwent exercise (voluntary running wheels) for 7 weeks and then remained sedentary for 4 weeks. At 15 weeks of age, offspring were euthanased and tissues collected for analysis. A reduction in adiposity, body weight, insulin, leptin and plasma triglycerides concentrations were observed in exercised offspring, despite increased food intake and these effects were maintained after 4 weeks of sedentary activity. Our findings demonstrate that early exercise intervention may have an impact on the adult metabolic state through modulation of hypothalamic FTO.This project provides evidence that early exercise intervention might have a protective effect on the adult metabolic profile following maternal obesity