Background

Events during pregnancy can increase birth weight (BW) and program glucose metabolism in the offspring, but the relationship between utero stress and the actions of leptin in the control of body weight is not well established. The aim of this study was to assess the effects of in utero stress on glucose tolerance test (GTT) and body weight / leptin ratio in 4-weeks-old male offspring from high fat diet (HFD) treated mothers.

Methods

Sprague Dawley females rats were divided into 2 groups and randomized in two different diets: Control Diet (CD group - 65% carbohydrate, 20% protein, 15% fat) and High Fat Diet (HFD group - 26% carbohydrate including sucrose, 16% protein, 58% fat) for 4 weeks before mating. Then, the females were mated with age-matched male rats. After weaning, the offspring were randomly assigned into 4 groups: CD-CD and CD-HFD (offspring from CD group treated with CD or HFD) or HFD-CD and HFD-HFD (offspring from HFD group treated with CD or HFD).

Results

Offspring from HFD group exhibited higher BW and higher 4 weeks-old weight compared to CD group: BW (g) 6.481 vs 5.985g (p<0.0001); 4 weeks old weight (g): 73.59 vs 63.13g (p<0.0001). We observe difference in GTT depending on dam’s diets. Upon comparison of the two groups assigned to CD after weaning, HFD-CD exhibited significantly higher glucose concentration at 15 min. after glucose injection compared to CD-CD (p=0.0046). At 4-weeks of age, HFD-HFD group exhibited elevated serum leptin concentrations as compared to CD-HFD group (p=0.0266) despite higher body weights, while no difference was observed between the CD-CD and HFD-CD groups.

Conclusions

We found that offspring from dams fed a HFD were insulin resistant and have altered the relationship between body weight and serum leptin concentration, which may justify the observed weight gain. Our data suggest that alterations in the set point around which leptin regulates body weight could arise through processes operative in utero.