%0 Journal Article %A Fabiën Hogema %A Ranran Dai %A Xiang Li %A Christos Rossios %A Fan Chung %A Ian Adcock %A Coen Wiegman %T High-fat diet in mice leads to amplified ozone-induced airway hyperresponsiveness (AHR), mitochondrial dysfunction and insulin resistance %D 2016 %R 10.1183/13993003.congress-2016.PA4664 %J European Respiratory Journal %P PA4664 %V 48 %N suppl 60 %X 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.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. %U