The impact of adipose eosinophils on diet-induced airway hyperresponsiveness in mice

<bold>Introduction:</bold> Adipose eosinophils exhibit an obesity-resistant effect and are associated with the inhibition of high fat diet (HFD)-induced hyperinsulinemia. Additionally, reducing circulating insulin has been linked to a decrease in obesity-related airway hyperresponsiveness. <bold>Aim:</bold> To determine if adipose tissue eosinophils protect against HFD-induced airway hyperresponsiveness and metabolic dysfunction. <bold>Methods:</bold> Transgenic mice with increased circulating eosinophils due to interleukin-5 expression in T cells (+IL5T) and WT mice were fed HFD or normal chow for 19 weeks. Body weight and fat, fasting insulin and glucose, and airway responsiveness to inhaled serotonin before and after vagotomy were measured. Orexin receptor mRNA expression was measured in nodose and jugular ganglia. Airway responsiveness to serotonin was also measured following acute administration of insulin to WT mice. <bold>Results:</bold> Both WT and +IL5T mice fed a HFD gained body weight and fat, however +IL5T mice gained less. WT mice, but not +IL5T mice, on HFD had significant increased fasting insulin and airway hyperresponsiveness before vagotomy. Moreover, acute insulin administration significantly increased serotonin-induced airway responsiveness in WT mice. Baseline eosinophils were increased in multiple tissues in +IL5T mice, and HFD selectively increased adipose tissue eosinophils. Orexin receptor 1 and 2 mRNA expression was decreased in +IL5T mice regardless of diet. <bold>Conclusions:</bold> The increased adipose eosinophils in +IL5T mice may mitigate hyperinsulinemia, thereby preventing airway hyperresponsiveness. Determining the mechanism of these events may aid in developing targeted therapies for obesity-related asthma.