title: Hyperleptinemia is associated with impaired pulmonary host defense.
abstract: We have previously reported that obesity attenuates pulmonary inflammation in both patients with acute respiratory distress syndrome (ARDS) and in mouse models of the disease. We hypothesized that obesity-associated hyperleptinemia, and not body mass per se, drives attenuation of the pulmonary inflammatory response and that this e_ect could also impair the host response to pneumonia. We examined the correlation between circulating leptin levels and risk, severity, and outcome of pneumonia in 2 patient cohorts (NHANES III and ARDSNet-ALVEOLI) and in mouse models of diet-induced obesity and lean hyperleptinemia. Plasma leptin levels in ambulatory subjects (NHANES) correlated positively with annual risk of respiratory infection independent of BMI. In patients with severe pneumonia resulting in ARDS (ARDSNet-ALVEOLI), plasma leptin levels were found to correlate positively with subsequent mortality. In obese mice with pneumonia, plasma leptin levels were associated with pneumonia severity, and in obese mice with sterile lung injury, leptin levels were inversely related to bronchoalveolar lavage neutrophilia, as well as to plasma IL-6 and G-CSF levels. These results were recapitulated in lean mice with experimentally induced hyperleptinemia. Our findings suggest that the association between obesity and elevated risk of pulmonary infection may be driven by hyperleptinemia.
authors.affiliation: Department of Respiratory Medicine, Maastricht University Medical Centre+, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht, Netherlands; Department of Medicine, University of Vermont College of Medicine, Burlington, Vermont, USA.
authors.forename: Niki D J
authors.initials: ND
authors.lastname: Ubags
authors.affiliation: Department of Medicine, University of Vermont College of Medicine, Burlington, Vermont, USA.
authors.forename: Renee D
authors.initials: RD
authors.lastname: Stapleton
authors.affiliation: Department of Respiratory Medicine, Maastricht University Medical Centre+, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht, Netherlands.
authors.forename: Juanita H J
authors.initials: JH
authors.lastname: Vernooy
authors.affiliation: Department of Medicine, University of Vermont College of Medicine, Burlington, Vermont, USA.
authors.forename: Elianne
authors.initials: E
authors.lastname: Burg
authors.affiliation: Department of Medicine, University of Vermont College of Medicine, Burlington, Vermont, USA.
authors.forename: Jenna
authors.initials: J
authors.lastname: Bement
authors.affiliation: Department of Medicine, University of Vermont College of Medicine, Burlington, Vermont, USA.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Hayes
authors.affiliation: Department of Medicine, University of Vermont College of Medicine, Burlington, Vermont, USA.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Ventrone
authors.affiliation: Flanders Institute for Biotechnology (VIB), Department of Medical Protein Research, Ghent University, Ghent, Belgium.
authors.forename: Lennart
authors.initials: L
authors.lastname: Zabeau
authors.affiliation: Flanders Institute for Biotechnology (VIB), Department of Medical Protein Research, Ghent University, Ghent, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Tavernier
authors.affiliation: Department of Medicine, University of Vermont College of Medicine, Burlington, Vermont, USA.
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Poynter
authors.affiliation: Department of Medicine, University of Vermont College of Medicine, Burlington, Vermont, USA.
authors.forename: Polly E
authors.initials: PE
authors.lastname: Parsons
authors.affiliation: Department of Medicine, University of Vermont College of Medicine, Burlington, Vermont, USA.
authors.forename: Anne E
authors.initials: AE
authors.lastname: Dixon
authors.affiliation: Department of Microbiology & Molecular Genetics, University of Vermont College of Medicine, Burlington, Vermont, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Wargo
authors.affiliation: Department of Medicine, University of Vermont College of Medicine, Burlington, Vermont, USA.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Littenberg
authors.affiliation: Department of Respiratory Medicine, Maastricht University Medical Centre+, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht, Netherlands.
authors.forename: Emiel F M
authors.initials: EF
authors.lastname: Wouters
authors.affiliation: Department of Medicine, University of Vermont College of Medicine, Burlington, Vermont, USA.
authors.forename: Benjamin T
authors.initials: BT
authors.lastname: Suratt