Reduction of Maternal Adiposity Attenuates Leptin Expression during Pregnancy in The Preeclamptic‐like BPH/5 Mouse

Abstract

Maternal adiposity and circulating leptin have been implicated in the pathogenesis of adverse pregnancy outcomes such as preeclampsia (PE), a pregnancy‐specific hypertensive disorder, and intrauterine growth restriction (IUGR). To better understand the role of leptin in PE, we utilized the obese BPH/5 mouse which spontaneously develops hypertension in late gestation, fetal demise, and IUGR. We have previously shown BPH/5 adult female mice are hyperphagic, hyperleptinemic, and leptin resistant prior to pregnancy. We hypothesized that BPH/5 females would also be hyperleptinemic during pregnancy with increased leptin expression from white adipose tissue (WAT) and the maternal‐fetal interface, which can be reduced by weight loss. To test our hypothesis, BPH/5 females were calorie restricted beginning at the time of conception, embryonic day (e) 0.5, by pair‐feeding the amount of normal chow consumed by age‐ and gestation‐matched ad libitum fed control C57 female mice. Pair‐feeding BPH/5 female mice reduced body weight significantly compared to ad libitum fed BPH/5 by e3.5 (n=6; p<0.05) and WAT mass by e10.5 (n=6; p<0.05). Circulating leptin was significantly higher in BPH/5 ad libitum fed pregnant mice vs C57 at e7.5 (n=4–5; p<0.05) and e18.5 (n=4–5; p<0.05), and pair‐feeding attenuated this at both time points (n=3–5; p<0.05). Furthermore, WAT leptin mRNA expression was significantly higher in ad libitum fed pregnant BPH/5 mice vs C57Bl/6 at e7.5 (n=6; p<0.05), and this was also attenuated by pair‐feeding (n=6; p<0.05). Interestingly, leptin mRNA expression was low and not statistically different between e7.5 implantation sites from ad libitum C57Bl/6 and BPH/5 dams, nor pair‐fed BPH/5 dams (n=6; p>0.05). However, by e18.5 placental leptin expression was significantly higher in ad libitum fed BPH/5 pregnant mice compared to C57Bl/6 at e18.5 (n=4; p<0.0001), and this was also attenuated by pair‐feeding (n=5; p<0.0001). Pair‐feeding BPH/5 female mice beginning two weeks before pregnancy and throughout increased live birth weight and litter sizes compared to BPH/5 ad libitum fed pregnancies (n=5; p<0.05). This improvement in fetal demise and IUGR was not shown when pair‐feeding began at e0.5 (n=6; p>0.05). Therefore, we believe that pre‐conception reduction in maternal adiposity and leptin may be critical for improving PE‐associated outcomes in this model. In summary, we demonstrated a reduction in both placenta and WAT leptin expression in BPH/5 pregnant female mice after weight loss. Future investigations are necessary to understand WAT and placental leptin expression during obese high‐risk pregnancies, and their relative contribution to the development of PE. This data holds translational potential as lifestyle interventions, including weight loss and adipose tissue reduction in women before pregnancy, may play a critical role in preventing adverse outcomes by decreasing the expression of adipokines, i.e. leptin, that are thought to contribute to the pathophysiology of PE.Support or Funding InformationVCS & SVM CORP (LSU), Louisiana Biomedical Collaborative Research ProgramThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.