Obesity, not a high fat, high sucrose diet alone, induced glucose intolerance and cardiac dysfunction during pregnancy and postpartum

Abstract

Cardiovascular disease is the leading cause of death in women during pregnancy and the postpartum period. Obesity is an independent risk factor for cardiovascular diseases. Nearly 60% of women of reproductive age are considered overweight or obese, cardiovascular disease morbidity and mortality continue to be pervasive. The objective of this study was to determine the effects of an obesogenic diet on the cardiometabolic health of dams during pregnancy and postpartum. Female mice were fed either a high-fat, high-sucrose diet (HFHS) or a refined control diet (CON) for 8 weeks before initiation of pregnancy and throughout the study period. Mice in the HFHS showed two distinct phenotypes, obesity-prone (HFHS/OP) and obesity resistance (HFHS/OR). Pre-pregnancy obesity (HFHS/OP) induced glucose intolerance before pregnancy and during postpartum. Systolic function indicated by the percent fractional shortening (%FS) was significantly decreased in the HFHS/OP at late pregnancy (vs. HFHS/OR) and weaning (vs. CON), but no differences were found at 6 weeks of postpartum among groups. No induction of pathological cardiac hypertrophy markers was found during postpartum. Plasma adiponectin was decreased while total cholesterol was increased in the HFHS/OP. Our results suggested that obesity, not the diet alone, negatively affected cardiac adaptation during pregnancy and postpartum.

Switching to a Standard Chow Diet at Weaning Improves the Effects of Maternal and Postnatal High-Fat and High-Sucrose Diet on Cardiometabolic Health in Adult Male Mouse Offspring

“…Second, the age and the strain of the mice were different: our mice were CD1 and studied at a later age (25 weeks old), while previous studies were younger C57BL/6 mice: 8 weeks [18] and 12 weeks [19]. Third, our mice in HH and HC were born from dams fed HFHS but not obese [10], in contrast to offspring in the previous studies which were from obese dams [18,19]. No induction of fetal genes and no changes in contractile proteins, such as myosin heavy chain composition, support our functional data.…”

“…We do not have a clear explanation, but we may speculate on several aspects: (1) A population-based prospective cohort study demonstrates that gestational weight gain is a strong predictor of the cardiometabolic health of offspring [21] and the absence of gestational weight gain in female mice could account for the minimal effects seen in the immediately subsequent generation [22]. Since dams of LL, HH, and HC were similar in BW, gestational weight gain, glucose tolerance, and lipid biomarkers [10], differences between LL and HH may not be observed. ( 2) Increased UPC3 protein levels in the hearts of HH may provide protective effects [23] that reduce reactive oxygen species production [24] which was shown here with no increase in lipid peroxidation.…”

“…Detailed physiological characteristics of dams, breeding schemes, and diet information were published previously [10]. Briefly, nulliparous female CD-1 mice were fed either a high-fat, high-sucrose diet (HFHS, 4.7 kcal/g with 45%, 15%, and 40% total calories from fat, protein, and carbohydrate, respectively, with 34% sucrose wt:wt, TD.08811, Envigo, Madison, WI, USA) or a refined low-fat, low-sucrose diet (LFLS, 3.8 kcal/g with 17%, 18%, and 64% total calories from fat, protein, and carbohydrate, respectively, with 12% sucrose wt:wt, TD.170522, Envigo, Madison, WI, USA) for eight weeks before initiation of pregnancy, during gestation, and lactation.…”

“…Following 8 weeks of HFHS diet, half of the mice were obese and the other half were obese resistant. In this study, we used male offspring born from obese resistant dams [10] to determine maternal diet effect independent of maternal obesity. At postnatal day 21, all male mice were weaned into 3 groups: offspring born from maternal LFLS and postnatal LFLS (LL), maternal HFHS and postnatal HFHS (HH), and maternal HFHS weaned onto a standard laboratory chow diet (HC; Pico-Lab Select Rodent 50 IF/6F, 5V5R, Lab Diet, Fort Worth, Texas, USA), all studied at 5-6 months of age.…”

“…In addition, maternal obesity or maternal nutritional stress with a Western-style diet without obesity has elicited contradictory results in offspring health outcomes [2]. Thus, the objective of this study was to investigate the effects of maternal and postnatal diet on glucose metabolism, cardiac function, and mitochondrial respiration in male mouse adult offspring born from maternal HFHS dams without obesity, which allowed us to examine the diet effect alone [10]. We tested the hypothesis that switching to a standard chow diet at weaning would attenuate systemic metabolic disorders and cardiac and mitochondrial dysfunction associated with maternal and postnatal HFHS diet in adult male mouse offspring.…”