title: Leptin does not influence surfactant synthesis in fetal sheep and mice lungs.
abstract: In the fetus, leptin in the circulation increases at late gestation and likely influences fetal organ development. Increased surfactant by leptin was previously demonstrated in vitro using fetal lung explant. We hypothesized that leptin treatment given to fetal sheep and pregnant mice might increase surfactant synthesis in the fetal lung in vivo. At 122-124 days gestational age (term: 150 days), fetal sheep were injected with 5 mg of leptin or vehicle using ultrasound guidance. Three and a half days after injection, preterm lambs were delivered, and lung function was studied during 30-min ventilation, followed by pulmonary surfactant components analyses. Pregnant A/J mice were given 30 or 300 mg of leptin or vehicle by intraperitoneal injection according to five study protocols with different doses, number of treatments, and gestational ages to treat. Surfactant components were analyzed in fetal lung 24 h after the last maternal treatment. Leptin injection given to fetal sheep increased fetal body weight. Control and leptin-treated groups were similar in lung function (preterm newborn lamb), surfactant components pool sizes (lamb and fetal mice), and expression of genes related to surfactant synthesis in the lung (fetal mice). Likewise, saturated phosphatidylcholine and phospholipid were normal in mice lungs with absence of circulating leptin (ob/ob mice) at all ages. These studies coincided in findings that neither exogenously given leptin nor deficiency of leptin influenced fetal lung maturation or surfactant pool sizes in vivo. Furthermore, the key genes critically required for surfactant synthesis were not affected by leptin treatment.
authors.affiliation: Division of Pulmonary Biology, Cincinnati Children’s Hospital Medical Center, University of Cincinnati, Ohio, 45229-3039, USA.
authors.forename: Atsuyasu
authors.initials: A
authors.lastname: Sato
authors.forename: Angelica
authors.initials: A
authors.lastname: Schehr
authors.forename: Machiko
authors.initials: M
authors.lastname: Ikegami
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000187:drug effects; D005260:Female; D005333:Fetus / Q000187:drug effects* / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D020738:Leptin / Q000008:administration & dosage / Q000494:pharmacology*; D008168:Lung / Q000033:anatomy & histology / Q000187:drug effects* / Q000196:embryology* / Q000378:metabolism; D051379:Mice; D008820:Mice, Obese; D009929:Organ Size / Q000187:drug effects; D010713:Phosphatidylcholines / Q000378:metabolism; D011247:Pregnancy; D037661:Pulmonary Surfactant-Associated Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D012756:Sheep / Q000196:embryology*
chemical_list: D020738:Leptin; D010713:Phosphatidylcholines; D037661:Pulmonary Surfactant-Associated Proteins