The impact of eosinophilia on high fat diet-induced obesity and airway hyperresponsiveness

Abstract

Hypothesis/Rationale: Eosinophils contribute to both adipose tissue metabolic homeostasis in obesity and airway hyperresponsiveness in asthma, but the role of eosinophils in obesity-related airway hyperresponsiveness is not understood. Considering that metabolic disorders increase the susceptibility to airway hyperresponsiveness in obese individuals, we investigated whether adipose eosinophils play a protective role in obesity-related airway hyperresponsiveness. Methods: Wild type (WT) and transgenic mice that overexpress interleukin 5 in peripheral T cells (+IL5T) were fed a high fat (61.6% fat) or normal chow (13.6% fat) diet for 19 weeks. Body weight, body fat, fasting glucose and insulin, and bronchoconstriction in response to inhaled serotonin were measured. The number of eosinophils were counted using flow cytometry in lung, adipose, and blood from transgenic WT and +IL5T mice with GFP-expressing eosinophils. Data: High fat diet significantly increased body weight and body fat in both WT and +IL5T mice, however +IL5T mice gained less weight and body fat than the WT mice. High fat diet increased fasting glucose, fasting insulin, and nerve-mediated airway responsiveness to inhaled serotonin in only the WT mice. On a normal chow diet, +IL5T mice had significantly more eosinophils in lung, blood, and adipose, and high fat diet further increased eosinophils in +IL5T adipose tissue. Acute administration of 1.29 U/kg (i.p.) insulin to a WT mouse on a normal chow diet significantly potentiated airway hyperresponsiveness to inhaled serotonin. Summary of results: Eosinophils in adipose tissue prevented high fat diet increases in circulating glucose and insulin, resulting in less body weight and body fat. This reduction in insulin by eosinophils in adipose tissue prevented obesity-related airway hyperresponsiveness. Conclusions: Insulin is a key modulator of obesity-related airway hyperresponsiveness. Eosinophils in adipose tissue play an important role in preventing obesity-related airway hyperresponsiveness by modulating insulin levels. Funding: NIH HL164474, NIH HL163087. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.