TY - JOUR T1 - High-fat diet in mice leads to amplified ozone-induced airway hyperresponsiveness (AHR), mitochondrial dysfunction and insulin resistance JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.congress-2016.PA4664 VL - 48 IS - suppl 60 SP - PA4664 AU - Fabiën Hogema AU - Ranran Dai AU - Xiang Li AU - Christos Rossios AU - Fan Chung AU - Ian Adcock AU - Coen Wiegman Y1 - 2016/09/01 UR - http://erj.ersjournals.com/content/48/suppl_60/PA4664.abstract N2 - 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. ER -