Abstract
It is estimated that 30% of pregnant women worldwide are overweight or obese, leading to adverse health effects for both 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 challenged with HE diet prior to mating and bred according to their propensity to gain weight. The original outbred breeding dams (F0) were maintained on low-fat chow during pregnancy and lactation. By comparison, the F1 dams consuming HE diet during pregnancy and lactation displayed higher gestational body weight gain (P < 0.01), and HE diet caused increased meal size and reduced meal frequency (P < 0.001). Sensitivity to the hormone amylin was preserved during pregnancy, regardless of diet. After several rounds of selective breeding, DIO and DR dams from generation F3 were provided chow or HE during pregnancy and lactation and 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 (P < 0.001). A high-resolution analysis of maternal behaviors did not detect main effects of diet or phenotype, but a subset of DIO dams showed delayed nursing behavior (P < 0.05). In generation F6/F7 dams, effects on gestational weight gain persisted (P < 0.01), and we observed a main effect of phenotype during a sucrose preference test (P < 0.05), with DIO-chow dams showing lower sucrose preference than DR controls (P < 0.05). Both DIO and DR dams consuming HE diet had hepatic steatosis (P < 0.001) and exhibited reduced leptin sensitivity in the arcuate nucleus (P < 0.001). These data demonstrate that both diet and genetic obesity-proneness have consequences on maternal health.
Highlights
Female reproductive health and metabolic status are strongly interconnected
While it is documented that women who are overweight or obese during pregnancy are at a higher risk for developing both metabolic and mental disorders, including increased insulin resistance in early pregnancy, gestational diabetes mellitus, hypertension, pre-eclampsia and postpartum depression (Molyneaux et al, 2014; Marchi et al, 2015; Catalano and Shankar, 2017; Kumpulainen et al, 2018), rodent models of maternal obesity have been used less frequently to investigate the precise nature of the biological link between obesity-related factors and the increased risk for these maternal diseases
The results are presented in three parts, each representing the observations made from dams in the early stage of selective breeding (F0 and F1 dams), mid-stage of selective breeding (F3 dams), and later stages of selective breeding (F6 and F7 dams)
Summary
Female reproductive health and metabolic status are strongly interconnected. Sufficient energy stores are permissive of ovulation, while pregnancy and lactation represent two metabolically dynamic periods of a female’s life when both the levels of and receptivity to gonadal, placental and metabolic hormones are changing rapidly. Proposed by Barker in the late 20th century (The International Society for Developmental Origins of Health and Disease, 2003; Barker, 2007), the developmental origins of health and disease hypothesis (DOHaD) suggests that the maternal environment impacts the long-term health and wellbeing of the offspring. Consistent with this hypothesis, maternal obesity is a significant predictor for childhood obesity, and increases the risk for metabolic syndrome and cardiovascular disease in the offspring later in life (Strauss and Knight, 1999; Catalano et al, 2009; Shrestha et al, 2021). While it is documented that women who are overweight or obese during pregnancy are at a higher risk for developing both metabolic and mental disorders, including increased insulin resistance in early pregnancy, gestational diabetes mellitus, hypertension, pre-eclampsia and postpartum depression (Molyneaux et al, 2014; Marchi et al, 2015; Catalano and Shankar, 2017; Kumpulainen et al, 2018), rodent models of maternal obesity have been used less frequently to investigate the precise nature of the biological link between obesity-related factors and the increased risk for these maternal diseases
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