Obesity exacerbates allergic airway inflammation and impairs lung function in Brown Norway rats

Abstract Obesity is a comorbidity that worsens asthma control and lung mechanics. We evaluated whether diet-induced obesity (high-fat high-carbohydrate diet (HFHC) modifies allergic airway inflammation induced by house dust mite (HDM) sensitization in Brown Norway rats, using repeated double-chamber plethysmography (DCP) over time. Male Brown Norway rats were fed with control chow or HFHC diet for 15 weeks. After 8 weeks, animals were sensitized via subcutaneous HDM injections then challenged intranasally (or vehicle). Lung function was assessed at four time points via DCP. Metabolic profiling (glucose, insulin, HOMA-IR, leptin, cholesterol, triglycerides, NEFA), serum and BALF IL-6, adiposity indices, histology and eosinophil counts were measured. Two-way ANOVA (diet × HDM) with Tukey post-hoc testing was used. HFHC diet increased adiposity and altered metabolic markers (elevated glucose, cholesterol, NEFA, insulin). HFHC diet and HDM sensitization independently reduced tidal volume (TV), expired volume (EV), minute ventilation (MV), PIF/PEF, and mid-expiratory flow (EF50), with the greatest impairment in HFHC/HDM animals. BALF IL-6 concentration increased after HDM challenge; histology revealed peribronchiolar inflammation and structural alterations in the airways. Changes in sRaw and sGaw were less consistent. HFHC diet-induced obesity exacerbates allergic airway inflammation and impairs ventilatory function in Brown Norway rats. This longitudinal non-invasive model recapitulates features of the obese-asthma phenotype and provides a platform for descriptive findings and characterization of the model.