Glucose metabolism dictates murine eosinophil differentiation, chemotaxis, and IL-4 expression

Abstract

RATIONALE: Obesity increases asthma severity. Weight loss in bariatric surgery improves asthma symptoms and reduces airway hyperresponsiveness. We hypothesized that vertical sleeve gastrectomy (VSG), a model of bariatric surgery, would reduce airway pathology in allergen-challenged obese mice. METHODS: Five-week old C57BL6 mice were fed a high fat diet (HFD -45% kcal fat) or normal chow and concurrently challenged with intranasal house dust mite (HDM) allergen (25 mg) or saline 3 days/week for 8 weeks. These challenged mice immediately underwent VSG or sham surgery, or no surgery (NS) as control (n55 per group). After one-week recovery, mice were returned to HFD and HDM challenges for four weeks. Twenty-four hours after the final HDM challenge, the mice were tested for airway responsiveness to increasing doses of methacholine delivered intravenously, and lung mechanics were evaluated using Flexivent (SciReq). Blood and bronchoalveolar lavage (BAL) with saline were collected. Harvested lung slices were stained with Masson's trichrome, Periodic acid Schiff or hematoxylin and eosin stains. Percent trichrome staining was quantified using Image J (NIH). Interleukin (IL)-13, IL-5, glucagon-like peptide-1, transforming growth factor-beta, insulin and leptin were measured in blood and/or lavage fluid using ELISA. RESULTS: VSG induced significant weight loss and reduction of plasma leptin levels (p<0.05). Airway reactivity to bronchoconstrictor, airway tissue inflammation and percent BAL eosinophils (13.3% NS, 4.7% sham, 0.8% VSG) were reduced in HFD-fed, HDM-challenged mice following VSG compared to sham or NS (p<0.05). CONCLUSIONS: Weight loss surgery in obese, chronically allergenchallenged mice induces metabolic changes associated with improved airway inflammation and resistance.