The role of eosinophils in airway hyperresponsiveness in diet-induced obese mice

Background: Eosinophils have been identified as important cells in metabolic homeostasis and are known to induce airway hyperresponsiveness, an abnormal bronchoconstriction response to inhaled stimuli. Obesity-related asthma is one state of metabolic dysfunction in which the heterogeneous activity of eosinophils in the lung and adipose tissue is not clear. Aim: To test if eosinophils affect obesity-related airway hyperresponsiveness and obesity status using a diet-induced obese mouse model. Methods: Wild type C57BL/6J mice (WT) and transgenic NJ1638 mice with systemic eosinophilia driven by high IL5 (+Eos) were fed a normal or high fat diet for 19 weeks. Food intake, body weight, body fat composition, and fasting glucose were measured. Airway responsiveness to inhaled serotonin, which induces vagally-mediated reflex bronchoconstriction, was tested in fasted, anesthetized, and ventilated mice. Results: Body fat and airway responses to aerosolized serotonin were similar between WT and +Eos mice fed a normal diet. When fed a high fat diet, WT and +Eos mice consumed similar amounts of food. Despite this, WT mice gained more weight, had higher body fat composition, and had higher fasting blood glucose than +Eos mice. WT mice on a high fat diet developed significant airway hyperresponsiveness to inhaled serotonin, while +Eos mice on a high fat diet did not. Conclusions: An increase in circulating eosinophils is associated with lower body fat composition and reduced airway responsiveness following a high fat diet. Eosinophils may have an underappreciated role in regulating body fat and may also protect against obesity-related airway hyperresponsiveness.