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High-fat diet in mice leads to amplified ozone-induced airway hyperresponsiveness (AHR), mitochondrial dysfunction and insulin resistance

Fabiën Hogema, Ranran Dai, Xiang Li, Christos Rossios, Fan Chung, Ian Adcock, Coen Wiegman
European Respiratory Journal 2016 48: PA4664; DOI: 10.1183/13993003.congress-2016.PA4664
Fabiën Hogema
1Pharmaceutical Sciences, University of Utrecht, Utrecht, Netherlands
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Ranran Dai
2Airway Disease, National Heart & Lung Institute, Imperial College London, London, United Kingdom
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Xiang Li
2Airway Disease, National Heart & Lung Institute, Imperial College London, London, United Kingdom
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Christos Rossios
2Airway Disease, National Heart & Lung Institute, Imperial College London, London, United Kingdom
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Fan Chung
2Airway Disease, National Heart & Lung Institute, Imperial College London, London, United Kingdom
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Ian Adcock
2Airway Disease, National Heart & Lung Institute, Imperial College London, London, United Kingdom
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Coen Wiegman
2Airway Disease, National Heart & Lung Institute, Imperial College London, London, United Kingdom
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Abstract

Rationale. COPD is characterised by chronic and progressive airway obstruction and associated with other conditions including obesity and diabetes. We determined the effects of high-fat feeding on airway inflammation and lung function in the chronic ozone mouse model.

Methods. Male C57BL/6 mice were fed a low- or high-fat diet for 10 weeks. During the last 6 weeks mice were exposed to ozone (3ppm) twice a week for 3 hours per exposure. An IPGTT was performed one day before the final ozone exposure. One day after the final exposure AHR was determined and BAL, plasma and tissue samples collected.

Results. High-fat feeding alone induced insulin resistance with a mild pulmonary inflammation consisting of elevated BAL cells (p<0.01) and increased IL-5, IFNγ and GM-CSF levels (p<0.05). This was associated with ROS accumulation (p<0.01) and mitochondrial dysfunction (p<0.01). Ozone exposure in combination with high-fat diet amplified AHR (p<0.05) and glucose and insulin responses (p<0.05). In addition, ozone and high-fat feeding resulted in higher mitochondrial ROS accumulation and a more profound mitochondrial dysfunction.

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Conclusion. Ozone-induced pulmonary inflammation, AHR and associated mitochondrial dysfunction are amplified during high-fat feeding. High-fat diets in man may enhance the effects of environmental pollution particularly in subjects with airways disease.

  • COPD - mechanism
  • Comorbidities
  • Animal models
  • Copyright ©the authors 2016
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High-fat diet in mice leads to amplified ozone-induced airway hyperresponsiveness (AHR), mitochondrial dysfunction and insulin resistance
Fabiën Hogema, Ranran Dai, Xiang Li, Christos Rossios, Fan Chung, Ian Adcock, Coen Wiegman
European Respiratory Journal Sep 2016, 48 (suppl 60) PA4664; DOI: 10.1183/13993003.congress-2016.PA4664

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High-fat diet in mice leads to amplified ozone-induced airway hyperresponsiveness (AHR), mitochondrial dysfunction and insulin resistance
Fabiën Hogema, Ranran Dai, Xiang Li, Christos Rossios, Fan Chung, Ian Adcock, Coen Wiegman
European Respiratory Journal Sep 2016, 48 (suppl 60) PA4664; DOI: 10.1183/13993003.congress-2016.PA4664
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