The Role of Leptin in Pulmonary Surfactant Production Using a Seal Model

Christina L. Grek1, John E. Baatz1,2, Ailsa J. Hall3, and John A. Hammond4

¹ Marine Biomedicine and Environmental Sciences Center, Medical University of South Carolina, Charleston, SC, USA

² Department of Pediatrics, Medical University of South Carolina, Charleston, SC, USA

³ Sea Mammal Research Unit, Gatty Marine Laboratory, University of St Andrews, St Andrews, Scotland

⁴ Stanford University, Departments of Structural Biology, Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA USA

Leptin, the product of the ob gene, is a circulating cytokine that has been characterized to be secreted primarily by adipocytes in correlation with body mass index and the control of energy balance. Recently leptin and the leptin receptor have been identified in fetal and adult pulmonary tissues. Evidence has been presented that leptin expression is of key importance in the stretch-induced signaling pathway that results in pulmonary surfactant production as well as in lung growth and maturation and in the direct stimulation of surfactant phospholipids. However, the leptin signaling pathway appears to be switched off after full lung development. Surfactant has a variety of physiological and immune functions that includes reducing alveolar surface tension and bacterial clearance. In diving marine mammals surfactant production is key to lung reinflation after collapse during long dives. After diving, seals have been shown to produce amplified surfactant amounts which can be further correlated to high pulmonary leptin protein expression. This suggests that adult seals retain the ability to secrete pulmonary leptin and further proposes the use of the seal lung as a model for human surfactant regulation. We hypothesize that pulmonary leptin expression directly modulates the production and expression of surfactant and is a critical component involved in maintaining human pulmonary health during birth as proposed by a seal model. Using in vivo and in vitro studies leptin, leptin receptor, and surfactant expression and production will be systematically characterized and evaluated by simulating various stressors including oxygen deprivation, carbon dioxide derived acidosis, steroid modulation and pressure variation. The ultimate results from these experiments will provide for insight into the source, triggering mechanisms and pathways by which leptin and associated surfactant expression is occurring.