Abstract
Eosinophils contribute to metabolic homeostasis and airway hyperresponsiveness, but their specific role in obesity-related airway hyperresponsiveness remains unclear. To address this, we used transgenic mice that overexpress interleukin-5 (IL-5) in peripheral T cells (+IL-5T) and wild-type controls. On a normal diet, +IL-5T and wild-type mice have similar body weight, body fat, and airway nerve-mediated reflex bronchoconstriction in response to inhaled serotonin. Feeding wild-type mice a 61.6% high-fat diet resulted in significantly increased body weight, body fat, fasting glucose, fasting insulin, and reflex bronchoconstriction induced by serotonin, which was blocked by vagotomy. In contrast, +IL-5T mice on a high-fat diet gained less body weight and fat than wild-type mice on the same diet and did not exhibit potentiation in fasting glucose, fasting insulin, or reflex bronchoconstriction induced by serotonin. Compared with wild-type mice, +IL-5T mice on normal diet had significantly more adipose tissue eosinophils, and this was further increased by high-fat diet. High-fat diet did not increase adipose tissue eosinophils in wild-type mice. Our findings suggest that adipose tissue eosinophils may play a role in regulating body fat, thereby reducing insulin, which is a mediator of obesity-related airway hyperresponsiveness. Thus, our data indicate adipose tissue eosinophils may be an important avenue for research in obesity-related asthma.NEW & NOTEWORTHY This study investigates how eosinophils influence systemic metabolism and airway function in obesity. Known for their immune functions, eosinophils also mitigate obesity-related hyperinsulinemia, reducing airway hyperresponsiveness in obese mice models. The findings suggest potential therapeutic strategies targeting the intricate interplay among neurons, eosinophils, and the endocrine system to alleviate asthma in obesity. This research provides novel insights into the critical neuro-immune-endocrine interactions essential for managing obesity-related asthma.