# Obesity Enhances Non-Th2 Airway Inflammation in a Murine Model of Allergic Asthma

## TL;DR

Obesity worsens asthma inflammation in mice through non-Th2 pathways, not by increasing typical allergic responses.

## Contribution

The study reveals that high-fat diets exacerbate asthma via non-Th2 and neutrophilic inflammation, not through Th2 mechanisms.

## Key findings

- HFD-fed mice showed greater inflammatory cell infiltration and more severe lung inflammation compared to ND-fed mice.
- HFD mice had increased neutrophilic infiltration and elevated non-Th2 cytokines like Il17, Tnfa, and Il-1b.
- Th2-related markers like IgE, eosinophils, and Th2 cytokines were not significantly different between HFD and ND groups.

## Abstract

Obese patients with asthma present with aggravated symptoms that are also harder to treat. Here, we used a mouse model of allergic asthma sensitised and challenged to house dust mite (HDM) extracts to determine whether high-fat-diet consumption would exacerbate the key features of allergic airway inflammation. C57BL/6 mice were intranasally sensitised and challenged with HDM extracts over a duration of 3 weeks. The impact of high-fat-diet (HFD) vs. normal diet (ND) chow was studied on HDM-induced lung inflammation and inflammatory cell infiltration as well as cytokine production. HFD-fed mice had greater inflammatory cell infiltration around airways and blood vessels, and an overall more severe degree of inflammation than in the ND-fed mice (semiquantitative blinded evaluation). Quantitative assessment of HDM-associated Th2 responses (numbers of lung CD4+ T cells, eosinophils, serum levels of allergen-specific IgE as well as the expression of Th2 cytokines (Il5 and Il13)) did not show significant changes between the HFD and ND groups. Interestingly, the HFD group exhibited a more pronounced neutrophilic infiltration within their lung tissues and an increase in non-Th2 cytokines (Il17, Tnfa, Tgf-b, Il-1b). These findings provide additional evidence that obesity triggered by a high-fat-diet regimen may exacerbate asthma by involving non-Th2 and neutrophilic pathways.