Obesity-induced adipokine imbalance impairs mouse pulmonary vascular endothelial function and primes the lung for injury.

Authors

Dilip Shah, Center for Translational Medicine and Jane and Leonard Korman Lung Center, Thomas Jefferson UniversityFollow
Freddy Romero, Center of Translational Medicine and Division of Pulmonary and Critical Care Medicine, Thomas Jefferson UniversityFollow
Michelle Duong, Center for Translational Medicine and Jane and Leonard Korman Lung Center, Thomas Jefferson University
Nadan Wang, Center for Translational Medicine and Jane and Leonard Korman Lung Center, Thomas Jefferson UniversityFollow
Bishnuhari Paudyal, Department of Radiology, Thomas Jefferson UniversityFollow
Benjamin T Suratt, Department of Medicine, University of Vermont College of Medicine
Caleb B Kallen, Department of Obstetrics and Gynecology, Thomas Jefferson University
Jianxin Sun, Center for Translational Medicine and Jane and Leonard Korman Lung Center, Thomas Jefferson UniversityFollow
Ying Zhu, Center for Translational Medicine and Jane and Leonard Korman Lung Center, Thomas Jefferson University; Department of Respiratory Medicine, Changhai Hospital, Second Military Medical University
Kenneth Walsh, Whitaker Cardiovascular Institute, Boston University School of Medicine
Ross Summer, Center for Translational Medicine and Jane and Leonard Korman Lung Center, Thomas Jefferson UniversityFollow

Document Type

Article

Publication Date

6-12-2015

Comments

This article has been peer reviewed. It was published in: Scientific Reports.

Volume 5, 12 June 2015, Article number 11362.

The published version is available at DOI: 10.1038/srep11362

Copyright © 2015 The Authors

Abstract

Obesity is a risk factor for the development of acute respiratory distress syndrome (ARDS) but mechanisms mediating this association are unknown. While obesity is known to impair systemic blood vessel function, and predisposes to systemic vascular diseases, its effects on the pulmonary circulation are largely unknown. We hypothesized that the chronic low grade inflammation of obesity impairs pulmonary vascular homeostasis and primes the lung for acute injury. The lung endothelium from obese mice expressed higher levels of leukocyte adhesion markers and lower levels of cell-cell junctional proteins when compared to lean mice. We tested whether systemic factors are responsible for these alterations in the pulmonary endothelium; treatment of primary lung endothelial cells with obese serum enhanced the expression of adhesion proteins and reduced the expression of endothelial junctional proteins when compared to lean serum. Alterations in pulmonary endothelial cells observed in obese mice were associated with enhanced susceptibility to LPS-induced lung injury. Restoring serum adiponectin levels reversed the effects of obesity on the lung endothelium and attenuated susceptibility to acute injury. Our work indicates that obesity impairs pulmonary vascular homeostasis and enhances susceptibility to acute injury and provides mechanistic insight into the increased prevalence of ARDS in obese humans.

Recommended Citation

Shah, Dilip; Romero, Freddy; Duong, Michelle; Wang, Nadan; Paudyal, Bishnuhari; Suratt, Benjamin T; Kallen, Caleb B; Sun, Jianxin; Zhu, Ying; Walsh, Kenneth; and Summer, Ross, "Obesity-induced adipokine imbalance impairs mouse pulmonary vascular endothelial function and primes the lung for injury." (2015). Center for Translational Medicine Faculty Papers. Paper 32.
https://jdc.jefferson.edu/transmedfp/32

PubMed ID

26068229