A high-fat, high-sugar diet impairs maternal metabolism throughout pregnancy and lactation in mice.

Prenatal exposure to maternal overweight and elevated glucose increases risk of cardiometabolic disease in offspring. Preclinical models such as the high-fat, high-sugar (HFHS) fed mouse allow mechanistic studies and testing of interventions, but it is first critical to understand the extent of exposures across early development. We therefore assessed the impacts of feeding a HFHS diet to C57Bl/6J mice for 11 weeks before mating and throughout pregnancy and lactation, on maternal weight, body composition, activity and energy expenditure, feeding behaviour, substrate utilisation and glucose metabolism. We also assessed the impacts of maternal diet on late gestation fetuses, neonates and early offspring growth. HFHS dams were fatter than controls with impaired glucose tolerance before mating and throughout pregnancy and lactation (P < 0.001). Dams also exhibited altered feeding behaviours, increased energy expenditure (light phase: P < 0.001, dark phase: P < 0.001) and a shift in fuel usage from carbohydrate to fat oxidation throughout pregnancy (lower respiratory exchange ratio: light phase: P = 0.002, dark phase: P < 0.001). Fetuses of HFHS dams were hyperglycaemic at gestational day 18 (P = 0.031). Altered patterns of offspring growth during lactation resulted in fatter pups at weaning. Consumption of a HFHS before and throughout pregnancy and lactation exposes offspring to changes in maternal metabolism in utero and throughout lactation. Since maternal impacts differ between studies, it is essential that these are characterised in each model to understand the critical factors that drive programming of offspring metabolism. KEY POINTS: Consumption of an obesogenic, high-fat, high-sugar (HFHS) diet impairs glucose tolerance during pregnancy, but how this impacts metabolic adaptations during pregnancy and lactation remains unclear. In the present study, consumption of a HFHS diet in mice increased adiposity and impaired glucose tolerance before mating and throughout pregnancy and lactation. HFHS consumption impacted metabolic adaptations to pregnancy, including failure to shift from fat to carbohydrate oxidation, reduced fat deposition and lower insulin secretion. These alterations in maternal metabolism during pregnancy resulted in fetal hyperglycaemia and altered patterns of offspring neonatal growth, resulting in offspring that were fatter at weaning. These findings have implications for metabolic health of both mothers and their offspring.