How the early life environment underlies sex differences in metabolic disease risk is not yet fully understood. Here we examined the effects of maternal high fat diet (HFD) on energy balance in male and female offspring.


Female C57BL6/J mice were fed control (17% calories from fat) or HFD (45% calories from fat) for 12 weeks prior to pregnancy and bred with lean males. At weaning, offspring were fed control or HFD, generating 4 groups: CC, CH, HC, and HH, where the first letter corresponds to maternal diet and the second to offspring diet. At 20 weeks of age, energy expenditure (EE; kcal/hr) was assessed in offspring using indirect calorimetry. ANCOVA with offspring total body weight as a covariate was used to examine the effect of maternal HFD.


In both male and female offspring,as expected, post-weaning HFD consumption was associated with reduced average respiratory exchange ratio (male: CC vs CH: 0.89 ± 0.02 vs. 0.82 ± 0.02; p<0.01; female: CC vs CH: 0.88 ± 0.01 vs 0.82 ± 0.02; p<0.01). In male offspring, when comparing the effect of maternal HFD (CC vs HC or HC vs HH), the covariate significantly predicted average energy expenditure (EE) for both comparisons (CC vs HC, p<0.05; HC vs HH, p = 0.05), while there was no significant effect of maternal HFD on EE. In female offspring, neither maternal diet nor the covariate were significantly associated with EE. In both male and female control-fed offspring, maternal HFD had no effect on body weight, while in HFD-fed offspring, males but not females exposed to maternal HFD were significantly heavier than males from control-fed dams (CH vs HH, male: p=0.04, female: p=0.27).


In both male and female offspring, post-weaning HFD but not maternal HFD is associated with increased fat oxidation. In the context of maternal HFD, the EE data from males suggest that offspring total body weight, and not maternal obesity may be driving offspring changes in energy expenditure. USDA ARIS Project 6026-51000-010-05S.