Maternal Obesity Has Little Effect on the Immediate Offspring but Impacts on the Next Generation

Abstract

Maternal obesity during pregnancy has been linked to an increased risk of obesity and cardiometabolic disease in the offspring, a phenomenon attributed to developmental programming. Programming effects may be transmissible across generations through both maternal and paternal inheritance, although the mechanisms remain unclear. Using a mouse model, we explored the effects of moderate maternal diet-induced obesity (DIO) on weight gain and glucose-insulin homeostasis in first-generation (F1) and second-generation offspring. DIO was associated with insulin resistance, hyperglycemia and dyslipidemia before pregnancy. Birth weight was reduced in female offspring of DIO mothers (by 6%, P = .039), and DIO offspring were heavier than controls at weaning (males by 47%, females by 27%), however there were no differences in glucose tolerance, plasma lipids, or hepatic gene expression at 6 months. Despite the relative lack of effects in the F1, we found clear fetal growth restriction and persistent metabolic changes in otherwise unmanipulated second-generation offspring with effects on birth weight, insulin levels, and hepatic gene expression that were transmitted through both maternal and paternal lines. This suggests that the consequences of the current dietary obesity epidemic may also have an impact on the descendants of obese individuals, even when the phenotype of the F1 appears largely unaffected.

Maternal high-fat diet acts as a stressor increasing maternal glucocorticoids’ signaling to the fetus and disrupting maternal behavior and brain activation in C57BL/6J mice

“…In the present study, no such association was registered between HFD and CD pups' weight at PND1. Although pups' gender was not taken into account, our data agree with those of King and colleagues who, while reporting a decrease in birth weight in HFD female pups, did not register a difference between HFD and CD males (King et al, 2013).…”

Childhood obesity: Current and novel approaches

“…These may have a small but significant effect across a population, and thus be cost-effective, but more intensive efforts in those susceptible to weight gain, with approaches such as interpersonal psychotherapy, may also be required [63]. Evidence from rodent studies suggests that the benefits of such an approach may have enormous implications in reducing the programming of later obesity and metabolic derangements in the offspring and future generations [64,65].…”

Early-life nutritional effects on the female reproductive system

“…Moreover, female offspring born to high-fat-fed dams produce oocytes with differentially methylated promoter regions of key metabolic genes (Ge et al 2014). It is not known if these epigenetic changes result in transgenerational effects; however, it has been recently shown in mice that high-fat diet-induced maternal obesity causes metabolic effects in F2 generation offspring via maternal inheritance (King et al 2013). However, It is unclear if these effects are germline-dependent or independent, which could be due to differential maternal adaptations to pregnancy in F1 offspring.…”