Abstract
Maternal nutrition during pregnancy is critical for foetal growth and development. In instances of suboptimal maternal diet, as is seen in scenarios of macronutrient restriction or overnutrition, foetal organ development becomes disrupted which can lead to a lifetime of impaired functioning and chronic disease. Although this offspring phenotype has been described by others in crude high/low intake versus control comparisons, most studies have failed to control for energy intake or changes in other macronutrients which may themselves affect the foetus. In this study, we used a nutritional geometry approach to investigate the effects of maternal intake of protein, carbohydrate, and fat during pregnancy on offspring metabolism and liver function in adulthood. Female C57Bl/6J mice (n=60) were habituated to one of ten isocaloric diets (i.e., differing in levels of protein, fat, and carbohydrates but with the same total energy), and then mated and allowed to give birth, at which point mothers were provided standard diet. The offspring (n=214) exposed to these specialised diets during foetal development were provided standard chow at weaning and observed to adulthood (15 weeks). Various functional assessments were made during life and metabolic tissues were collected at the study conclusion for analyses. We found that offspring of mothers fed low protein, low fat diets displayed lower bodyweight and impaired glucose metabolism at both weaning and adulthood. This effect was pronounced in males but were weaker in females. By adulthood, male but not female offspring of high protein-fed mothers also demonstrated depressed bodyweight. These findings suggest two things: firstly, that maternal protein intake and offspring health have a bimodal relationship whereby over- or undernutrition has detrimental effects on offspring metabolic function, and; secondly, that these effects differ depending on the sex of the offspring, with males typically displaying a more impaired metabolic phenotype. Results from proteomics analysis will also be presented, where we elucidate the proteomic changes in liver and heart tissue that underlie altered growth and metabolism under different diet exposures. This study is amongst the first to utilise nutritional geometry within a DOHaD (developmental origins of health and disease) context to tease apart the nuances of maternal macronutrient intakes on offspring organ development and later life health outcomes. By identifying an 'optimal' balance of macronutrients during pregnancy we can better understand how to optimise foetal organ development and provide the best start to life for our children.