Maternal high fat feeding and gestational dietary restriction: Effects on offspring body weight, food intake and hypothalamic gene expression over three generations in mice

Abstract

Excessive gestational weight gain and maternal obesity have both been associated with increased incidence of obesity and metabolic disorder in offspring in both humans and animal models. The objectives of this study were to determine (1) whether mild gestational food restriction during the third trimester (GFR) would alter food intake and growth parameters of offspring, (2) whether effects of GFR depended on diet (high fat [HF] vs chow), (3) whether effects of excessive gestational weight gain (WG) would become magnified across generations, and (4) whether diet and GFR would alter hypothalamic gene expression in adult offspring. Three generations of female C57BL/6 mice were fed chow or HF diet, mated at 11 weeks of age and assigned to ad libitum feeding or 25% GFR. Offspring were fed the same diet as their mothers. Results showed (1) maternal gestational WG was positively correlated with offspring WG. (2) HF offspring weighed less ( p < 0.01) at weaning (WWT) but gained more during the 8 weeks after weaning than chow-fed offspring ( p < 0.05), resulting in higher final body weights (BW) ( p < 0.01). (3) HF males from GFR mothers had higher WWT ( p < 0.05), but subsequent WG and final BW were less ( p < 0.05) compared to males from ad lib mothers. (4) In the HF group, GFR also resulted in decreased FI ( p < 0.05) and FE ( p < 0.07) in offspring, compared to offspring from ad lib mothers. (5) In generation 3, hypothalamic expression of tyrosine hydroxylase was lower in HF males from GFR mothers compared to HF males from ad lib mothers ( p < 0.05). In conclusion, gender and maternal GFR had independent effects on growth and FI, and hypothalamic gene expression was dependent on both gender and maternal GFR in HF offspring. Even mild food restriction of obese mothers during pregnancy may have beneficial effects in reducing the risk or degree of obesity in offspring.