skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Diet-induced obesity reprograms the inflammatory response of the murine lung to inhaled endotoxin

Abstract

The co-occurrence of environmental factors is common in complex human diseases and, as such, understanding the molecular responses involved is essential to determine risk and susceptibility to disease. We have investigated the key biological pathways that define susceptibility for pulmonary infection during obesity in diet-induced obese (DIO) and regular weight (RW) C57BL/6 mice exposed to inhaled lipopolysaccharide (LPS). LPS induced a strong inflammatory response in all mice as indicated by elevated cell counts of macrophages and neutrophils and levels of proinflammatory cytokines (MDC, MIP-1γ, IL-12, RANTES) in the bronchoalveolar lavage fluid. Additionally, DIO mice exhibited 50% greater macrophage cell counts, but decreased levels of the cytokines, IL-6, TARC, TNF-α, and VEGF relative to RW mice. Microarray analysis of lung tissue showed over half of the LPS-induced expression in DIO mice consisted of genes unique for obese mice, suggesting that obesity reprograms how the lung responds to subsequent insult. In particular, we found that obese animals exposed to LPS have gene signatures showing increased inflammatory and oxidative stress response and decreased antioxidant capacity compared with RW. Because signaling pathways for these responses can be common to various sources of environmentally induced lung damage, we further identified biomarkers that are indicative ofmore » specific toxicant exposure by comparing gene signatures after LPS exposure to those from a parallel study with cigarette smoke. These data show obesity may increase sensitivity to further insult and that co-occurrence of environmental stressors result in complex biosignatures that are not predicted from analysis of individual exposures. - Highlights: ► Obesity modulates inflammatory markers in BAL fluid after LPS exposure. ► Obese animals have a unique transcriptional signature in lung after LPS exposure. ► Obesity elevates inflammatory stress and reduces antioxidant capacity in the lung. ► Toxicant-specific biomarkers predict exposure independent of systemic inflammation.« less

Authors:
 [1]; ; ; ;  [1];  [2]; ; ;  [1]
  1. Pacific Northwest National Laboratory, Richland, WA 99352 (United States)
  2. Battelle Toxicology Northwest, Richland, WA 99352 (United States)
Publication Date:
OSTI Identifier:
22285247
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 267; Journal Issue: 2; Other Information: Copyright (c) 2012 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANTIOXIDANTS; BIOLOGICAL MARKERS; DIET; ENZYME IMMUNOASSAY; ENZYMES; INFLAMMATION; LUNGS; LYMPHOKINES; MACROPHAGES; METABOLIC DISEASES; MICE; OXYGEN; TOBACCO SMOKES

Citation Formats

Tilton, Susan C., E-mail: susan.tilton@pnnl.gov, Waters, Katrina M., Karin, Norman J., Webb-Robertson, Bobbie-Jo M., Zangar, Richard C., Lee, K. Monica, Bigelow, Diana J., Pounds, Joel G., and Corley, Richard A. Diet-induced obesity reprograms the inflammatory response of the murine lung to inhaled endotoxin. United States: N. p., 2013. Web. doi:10.1016/J.TAAP.2012.12.020.
Tilton, Susan C., E-mail: susan.tilton@pnnl.gov, Waters, Katrina M., Karin, Norman J., Webb-Robertson, Bobbie-Jo M., Zangar, Richard C., Lee, K. Monica, Bigelow, Diana J., Pounds, Joel G., & Corley, Richard A. Diet-induced obesity reprograms the inflammatory response of the murine lung to inhaled endotoxin. United States. doi:10.1016/J.TAAP.2012.12.020.
Tilton, Susan C., E-mail: susan.tilton@pnnl.gov, Waters, Katrina M., Karin, Norman J., Webb-Robertson, Bobbie-Jo M., Zangar, Richard C., Lee, K. Monica, Bigelow, Diana J., Pounds, Joel G., and Corley, Richard A. Fri . "Diet-induced obesity reprograms the inflammatory response of the murine lung to inhaled endotoxin". United States. doi:10.1016/J.TAAP.2012.12.020.
@article{osti_22285247,
title = {Diet-induced obesity reprograms the inflammatory response of the murine lung to inhaled endotoxin},
author = {Tilton, Susan C., E-mail: susan.tilton@pnnl.gov and Waters, Katrina M. and Karin, Norman J. and Webb-Robertson, Bobbie-Jo M. and Zangar, Richard C. and Lee, K. Monica and Bigelow, Diana J. and Pounds, Joel G. and Corley, Richard A.},
abstractNote = {The co-occurrence of environmental factors is common in complex human diseases and, as such, understanding the molecular responses involved is essential to determine risk and susceptibility to disease. We have investigated the key biological pathways that define susceptibility for pulmonary infection during obesity in diet-induced obese (DIO) and regular weight (RW) C57BL/6 mice exposed to inhaled lipopolysaccharide (LPS). LPS induced a strong inflammatory response in all mice as indicated by elevated cell counts of macrophages and neutrophils and levels of proinflammatory cytokines (MDC, MIP-1γ, IL-12, RANTES) in the bronchoalveolar lavage fluid. Additionally, DIO mice exhibited 50% greater macrophage cell counts, but decreased levels of the cytokines, IL-6, TARC, TNF-α, and VEGF relative to RW mice. Microarray analysis of lung tissue showed over half of the LPS-induced expression in DIO mice consisted of genes unique for obese mice, suggesting that obesity reprograms how the lung responds to subsequent insult. In particular, we found that obese animals exposed to LPS have gene signatures showing increased inflammatory and oxidative stress response and decreased antioxidant capacity compared with RW. Because signaling pathways for these responses can be common to various sources of environmentally induced lung damage, we further identified biomarkers that are indicative of specific toxicant exposure by comparing gene signatures after LPS exposure to those from a parallel study with cigarette smoke. These data show obesity may increase sensitivity to further insult and that co-occurrence of environmental stressors result in complex biosignatures that are not predicted from analysis of individual exposures. - Highlights: ► Obesity modulates inflammatory markers in BAL fluid after LPS exposure. ► Obese animals have a unique transcriptional signature in lung after LPS exposure. ► Obesity elevates inflammatory stress and reduces antioxidant capacity in the lung. ► Toxicant-specific biomarkers predict exposure independent of systemic inflammation.},
doi = {10.1016/J.TAAP.2012.12.020},
journal = {Toxicology and Applied Pharmacology},
number = 2,
volume = 267,
place = {United States},
year = {Fri Mar 01 00:00:00 EST 2013},
month = {Fri Mar 01 00:00:00 EST 2013}
}