Leptin Enhances Lung Maturity in the Fetal Rat

Abstract

Pulmonary alveolar type II cells synthesize and secrete phospholipids and surfactant proteins. In most mammalian species, the synthesis of phospholipids and proteins of lung surfactant increases with fetal lung maturation, which occurs late in gestation. Factors that may promote lung maturation and surfactant production include the placental hormone, leptin, whose expression increases with advancing gestational age. We demonstrate that physiologic concentrations of leptin (1 and 10 ng/mL) increase the levels of surfactant proteins (SP) A, B, and C mRNA as well as SP-A and SP-B protein in d-17 fetal rat lung explants in vitro. To determine whether leptin exerts similar effects in vivo, we administered leptin antenatally to pregnant rats and compared its effects to that of dexamethasone, a known mediator of fetal lung development. Antenatal treatment with leptin for 2 d significantly increased the average weight of the fetal lungs in relation to their body weight. Histologic analysis revealed that the increase in fetal lung weight was accompanied by an increase in the number and maturation of type II alveolar cells and the expression of surfactant proteins B and C in these cells. Collectively, these results suggest that leptin is a cytokine regulator of rat fetal lung maturity.

Obesity and Asthma

“…Previous reports have also shown that leptin and leptin receptor are expressed in airway epithelium (24), and bronchial expression of leptin is increased in chronic obstructive pulmonary disease (25,26). Leptin seems to be involved in embryonic lung growth and maturation (27,28), and in fibroproliferative responses in the lung to bleomycin (29). Furthermore, polymorphisms in leptin and leptin receptor have been associated with differences in lung function (30,31).…”

Postnatal leptin is necessary for maturation of numerous organs in newborn rats

“…This result contrasts with several studies carried out during fetal life, demonstrating an important role for leptin in the lung development of different species, such as rodents or primates. 29,30 At that stage, leptin receptors have been identified in the pneumocyte type II cells, which are responsible for synthesizing pulmonary surfactant and are developmentally regulated during late phases of gestation. 29,30 The lack of efficacy of leptin blockage during our study may suggest that its action on lung maturity is probably restricted to the gestational period in normal animals.…”

“…29,30 At that stage, leptin receptors have been identified in the pneumocyte type II cells, which are responsible for synthesizing pulmonary surfactant and are developmentally regulated during late phases of gestation. 29,30 The lack of efficacy of leptin blockage during our study may suggest that its action on lung maturity is probably restricted to the gestational period in normal animals. However, in IUGR animals, postnatal leptin treatment may be effective in correcting developmental defects in the lungs as suggested by our previous study performed in IUGR piglets.…”

Developmental Regulation of NO-Mediated VEGF-Induced Effects in the Lung

“…We detected SP-B (45 kD) and C (21 kD) protein from lung lysates using Western analysis undertaken with antibodies that reacted selectively with SP-B and SP-C (Abcam Inc., Cambridge, MA) and with b-tubulin (Santa Cruz Biotechnology, Santa Cruz, CA) as control, as previously described (20,21).…”