The early origins of obesity: the importance of prenatal vs postnatal environment.

Abstract

There is growing evidence that maternal obesity, maternal hyperglycemia or maternal intake of diets high in fat, sugar or total calories during pregnancy and lactation is associated with an increased risk of obesity and metabolic diseases in the offspring. The majority of studies to date, however, have examined the impact of maternal overnutrition during the entire perinatal period. While a small number of studies have provided clues that the impact of exposure to nutritional excess before birth in comparison to exposure during the early postnatal period may not be equivalent, the results of these studies have been inconsistent. Therefore, the relative contribution of prenatal and postnatal nutritional environment to obesity risk in the offspring remains unclear. The central aim of this thesis was to investigate the separate contributions of exposure to a maternal cafeteria diet during the prenatal and suckling periods on the metabolic outcomes of the offspring, specifically body weight, fat mass and the expression of key adipogenic and lipogenic genes at weaning, in early adolescence and in young adulthood using a cross-fostering approach in a rat model. The results of this thesis demonstrated that exposure to a maternal cafeteria diet during the suckling period is more important for determining fat mass at weaning than exposure before birth. Importantly, this thesis provided considerable evidence to suggest that exposure to a nutritionally-balanced diet during the suckling period has the capacity to prevent the negative effects of exposure to a high-fat/high-sugar diet before birth. In addition, this thesis has demonstrated that the effects of being exposed to a high-fat/high-sugar diet during the perinatal period on offspring adiposity could be reversed/controlled by consuming a nutritionally-balanced diet post-weaning. The results of this thesis also demonstrated that the levels of total fat, saturated and trans fats and omega-6 polyunsatured fatty acids (n-6 PUFA) in the dams milk were directly related to their levels in the maternal diet, and were higher in dams consuming a cafeteria diet. This supported the hypothesis that altered fat content and fatty acid composition of the milk is likely to play an important role in mediating the effects of maternal cafeteria diets on offspring fat mass, and may well account for the higher adiposity at weaning in offspring suckled by cafeteria-diet fed dams. Exposure to a cafeteria diet during the suckling period also resulted in altered expression of key adipogenic and lipogenic genes in visceral and subcutaneous fat depots and an increased susceptibility to diet-induced obesity in females. Importantly, this thesis provided evidence of clear sex-differences in the relative impact of prenatal and postnatal nutritional exposures on adipocyte gene expression and the susceptibility to diet-induced obesity in the offspring, suggesting that the timing of nutritional interventions aimed to re-program the offspring may be different in males and females. Overall, this thesis identifies the early postnatal period in rodents as a “critical window‟ for the programming of fat mass and susceptibility to diet-induced obesity in the offspring, and has provided important insights into the mechanisms underlying the early origins of obesity.