Abstract P230: Prevention Of Maternal Obesity Attenuates Adverse Offspring Cardiometabolic Outcomes In Preeclamptic-like Mouse Model

Abstract

Preeclampsia (PE) is a hypertensive disorder of pregnancy and a leading cause of maternal and fetal mortality with maternal obesity as a risk factor. Decreasing white adipose tissue (WAT) via calorie restriction during the first half of pregnancy may alter the maternal-fetal environment to improve offspring outcomes. We hypothesized that pair-feeding BPH/5 dams during pregnancy will improve cardiometabolic risk and WAT pro-inflammatory cytokine expression in BPH/5 offspring in a sex-dependent manner. Previously, we showed that BPH/5 males, unlike females, have similar body weights, daily food intake, and circulating leptin levels as compared to age-matched control mice. Although, adult BPH/5 females and males have cardiomegaly and increased subcutaneous and peri-renal WAT mass compared to lean control mice. To investigate the prevention of maternal obesity on offspring outcomes, BPH/5 dams were pair-fed (PF) beginning at embryonic day (e)0.5 to C57 pregnant mice. Offspring cardiometabolic risk and WAT pro-inflammatory cytokine mRNA were measured using real time PCR in adult ad libitum fed offspring. Compared to controls, peri-renal WAT from BPH/5 males showed a 5-fold increase while females had a 15-fold increase in TNFa (n=3-6; p<0.05), 6-fold increase in PTGS-2 for males and 5-fold increase for females (n=3-6; p<0.05), and 3-fold increase in IL-6 for males and 1.25-fold increase for females (n=3-6; p<0.05) in subcutaneous WAT. Adult offspring born to PF BPH/5 dams had decreased expression in TNFa (male: 4-fold and female: 7-fold), PTGS-2 (male: 5-fold and female: 4-fold), and IL-6 (male: 10-fold; n=3-6; p<0.05). In conclusion, prevention of maternal obesity in BPH/5 dams attenuates cardiometabolic risks and reduces the pro-inflammatory WAT milieu in male and female offspring. The transgenerational effects during pregnancy is believed to be caused by an alteration in the maternal-fetal environment due to WAT pro-inflammatory adipokines. Future investigations are necessary to understand the differences observed in BPH/5 male versus female mice into adulthood as well as the transgenerational impact of attenuated maternal obesity in pregnancy.