Premium
Pre‐Conception Leptin Resistance Characterizes the BPH/5 Mouse Model of Preeclampsia
Author(s) -
Sutton Elizabeth F,
Lob Heinrich E,
Liu ChinChi Liford,
Redman Leanne M,
Davisson Robin L,
Sones Jenny Liford
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.692.5
Subject(s) - leptin , medicine , preeclampsia , endocrinology , proteinuria , gestation , fetus , pregnancy , obesity , adipose tissue , metabolic syndrome , biology , kidney , genetics
Preeclampsia (PE) is a devastating disorder of pregnancy that presents with maternal hypertension and proteinuria after 20 weeks of gestation. Despite being a leading cause of maternal and fetal morbidity/mortality, the underlying mechanisms are unknown. PE is often described as an overall increased inflammatory state without a clear cause, and pre‐conception obesity has been proposed as a risk factor. Women with an elevated body mass index (>35 kg/m2) at conception have a 30% increased risk of developing PE compared to lean counterparts. We utilized the obese BPH/5 mouse model to investigate pre‐conception risk factors that may contribute to PE. BHP/5 mice are hyperphagic, have increased white adipose tissue (WAT), and spontaneously develop the maternal syndrome of hypertension and proteinuria, as well as the poor fetoplacental outcomes associated with PE. Reduction of WAT through pair‐feeding matched with C57BL/6 mice resulted in improved fetoplacental outcomes in late gestation. These improvements led us to hypothesize that obese BPH/5 female mice have derangements in leptin signaling contributing to their adverse metabolic phenotype and their risk of developing PE. To test this, female, virgin BPH/5 and C57BL/6 mice were fed an ad libitum standard chow diet and studied at 6–12 weeks of age. BPH/5 mice had significantly more circulating leptin as compared to C57BL/6 mice (12,600±3098 vs. 1165±271 pg/mL; n=4–6, p<0.05). Following three days of leptin administration (i.p., 30μg twice a day), BPH/5 mice exhibited severely blunted reductions in body weight (<5% v 10% in C57BL/6; n=4–6, p<0.05). Furthermore, food intake in BPH/5 remained significantly elevated as compared to C57BL/6 (n=4–6, p<0.05). Taken together this data suggests BPH/5 mice are leptin resistant. Chronic hyperleptinemia has been shown to characterize other models of PE; however, the preexisting maternal metabolic profile prior to pregnancy has not been fully understood as it relates to the pathogenesis of PE. Further studies will involve challenging the physiologic metabolic state of BPH/5 mice through pair‐feeding to reduce WAT before pregnancy and determining its effect on inflammation, placentation, and hypertension during gestation.