Influence of high energy diet and polygenic predisposition for obesity on postpartum health in rat dams

Abstract

It is estimated that 30% of pregnant women worldwide are overweight or obese, which leads to adverse health effects for both the mother and child. Women with obesity during pregnancy are at higher risk for developing both metabolic and mental disorders, such as diabetes and depression. Numerous studies have used rodent models of maternal obesity to understand its consequences on the offspring, yet characterization of changes in the dams is rare, and most rodent models rely solely on a high fat diet to induce maternal obesity, without regarding genetic propensity for obesity. Here we present the influence of both peripartum high energy diet (HE) and obesity-proneness on maternal health using selectively-bred diet-resistant (DR) and diet-induced obese (DIO) rat dams. Outbred Sprague-Dawley rats were selected and bred according to their propensity to gain weight. From F1 onward, dams consuming a HE diet displayed higher body weight gain during pregnancy, and HE diet had a strong effect on meal patterns. Sensitivity to the hormone amylin was preserved during pregnancy, regardless of diet. After several rounds of selective breeding, dams from generation F3 were assessed for their postpartum physiology and behaviors. We observed strong diet and phenotype effects on gestational weight gain, with DIO-HE dams gaining 119% more weight than DR-chow. A high-resolution analysis of maternal behaviors on postpartum day 2 (P2) did not detect main effects of diet or phenotype, but a subset of DIO dams showed decreased pup-related behaviors. During a sucrose preference test (SPT) on P14, all DR dams consumed at least 70% sucrose, while a subset of DIO dams preferred water. In generation F6/F7 dams, effects on gestational weight gain persisted, and we observed a main effect of phenotype on SPT, with DIO-chow dams showing the lowest sucrose preference. Both DIO and DR dams consuming HE diet had severe postpartum liver lipidosis and exhibited reduced leptin sensitivity in the arcuate nucleus at the time of pup-weaning. These data demonstrate that both diet and genetic obesity-proneness have consequences on maternal health.