Prenatal stress and nutrition effects on metabolic phenotype of offspring.

Abstract

The intrauterine environment can have profound effects on the development and health of offspring. Alteration in maternal nutritional status and prenatal stress has long-term consequences on offspring development and behavior. However, the mechanisms responsible for these changes are unclear. Pregnant female Sprague-Dawley rats were maintained on standard chow (CHOW) or 60% high-fat (HF) diet throughout gestation and lactation. Half of each group were exposed to a novel variable stress paradigm (STRESS) during the third week of gestation while control dams were left undisturbed (CON). One male pup was randomly selected from each litter for each postnatal test. Insulin content of milk was increased in dams on HF diet and this effect was enhanced by STRESS. Pups from dams’ that experienced prenatal stress and/or were on HF diet weighed more beginning on postnatal day 7 compared to CHOW-CON. HF diet at weaning appeared to enhance this effect through adulthood. Body composition analysis showed that the increased body weight was attributable to greater adiposity. When challenged with an oral glucose tolerance test, males weaned on CHOW diet showed no difference in glucose clearance or insulin secretion. However, males weaned on HF diet had impaired glucose tolerance if their dams were on HF diet, experienced prenatal stress, or both. Our data suggest that the intrauterine and postnatal environment is affected by prenatal stress and/or maternal nutrition in a manner that increases the susceptibility of offspring to diet-induced obesity and may lead to adverse metabolic consequences on HF diet. Support: NIH HD055030, DK077623.