1. Hyperleptinemia is associated with impaired pulmonary host defense
- Author
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Benjamin T. Suratt, Jan Tavernier, Catherine M. Hayes, Renee D. Stapleton, Niki D.J. Ubags, Matthew J. Wargo, S. Ventrone, Matthew E. Poynter, Emiel F.M. Wouters, Elianne Burg, Polly E. Parsons, Benjamin Littenberg, Juanita H. J. Vernooy, Anne E. Dixon, Lennart Zabeau, Jenna Bement, Pulmonologie, RS: NUTRIM - R3 - Chronic inflammatory disease and wasting, Promovendi NTM, and MUMC+: MA Longziekten (3)
- Subjects
0301 basic medicine ,medicine.medical_specialty ,ARDS ,Lung injury ,03 medical and health sciences ,0302 clinical medicine ,Insulin resistance ,Community-acquired pneumonia ,Internal medicine ,medicine ,medicine.diagnostic_test ,business.industry ,Leptin ,digestive, oral, and skin physiology ,Respiratory infection ,General Medicine ,medicine.disease ,3. Good health ,respiratory tract diseases ,Pneumonia ,030104 developmental biology ,Bronchoalveolar lavage ,Endocrinology ,030228 respiratory system ,Immunology ,business ,hormones, hormone substitutes, and hormone antagonists ,Research Article - 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 effect 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.
- Published
- 2016