It is well accepted that in utero exposure to maternal diet can program offspring development and susceptibility to disease in later life. While animal diet studies have focused on either maternal under-nutrition (e.g., calorie or protein restriction), or over-feeding of high fat diets, little is known about the effects of maternal dietary macronutrient balance (the proportions of protein, fat, and carbohydrate) in modulating offspring health. An important model called protein leverage explains that in many animals, including humans, protein is prioritised over carbohydrates and fats when confined to imbalanced diets. This tight, innate regulation of protein intake, influenced by dynamic protein targets, can result in the overconsumption of fats and carbohydrates when given protein-poor diets, leading to obesity and related co-morbidities. However, the question remains as to when and how this is programmed in an individual.
We hypothesise that protein targets are determined in utero and through early life programming. Using a mouse model, we investigate how maternal protein to carbohydrate (P:C) balance influences offspring appetite and metabolic health. We show that offspring from dams fed high P:C diets throughout gestation and lactation have greater protein targets and increased body weights in early life, consistent across sexes. We also show that these greater protein targets increase offspring food intake when placed on no-choice diets, resulting in an overall increase in body weight and fat mass. The combination of a high protein maternal diet and a Western diet in adulthood is revealed to further exacerbate this phenotype. The interaction of maternal and adult diets is also shown in outcomes such as plasma FGF21 and cholesterol levels, and overall activity and behaviour. This work highlights novel discoveries linking the intricate interaction of maternal nutrition, early-life programming and nutritional targets on long-lasting offspring consequences, providing fundamental new understanding to the field.