The Impact of Diet-induced Obesity on Allergic Lung Inflammation in Murine Models of Asthma

Obesity and asthma are major global health issues that are becoming more prevalent. Clinical studies indicate that obesity alters asthma pathology. Asthmatic patients who are obese suffer from severe and frequent exacerbations that are difficult to control using classical asthma medications, which in turn affects their quality of life. Few preclinical studies assessing the impact of obesity on asthma have investigated the underlying mechanisms, yet the effect of obesity is still controversial. My main hypothesis is that obesity has a negative effect on asthma by modulating the profile of allergic inflammation in the airways leading to worsening of symptoms and/or reduced response to therapies.

Experimental strategy: Allergen-induced lung inflammation was compared in C57BL/6 mice fed either a high-fat diet (HFD group) or standard mice chow (ND group) by investigating the extent of lung inflammation, cell types involved, main cytokines and mediators as well as airway remodelling. The current study developed a murine model of allergic asthma using a clinically relevant allergen called house dust mite (HDM) extract, administered only via the intranasal route. Phosphate buffered saline (PBS) instilled mice served as controls.

Main findings: The degree of HDM-induced airway inflammation was more severe in mice fed HFD than in the ND group, characterized by a significant increase in neutrophilic infiltration. Compared to OVA-induced pulmonary inflammation, mice fed HFD had more severe inflammation and mucus with increased infiltration of both eosinophilic and neutrophilic cell types. In addition, in the HDM model, expression of Th2 cytokines was not affected by HFD. Simultaneously, IL-17, TNFα, MCP-1, TGF-β, IL-1β were markedly upregulated, suggesting that this model that used a more clinical allergen diet-induced obesity modulates asthma via non-Th2, and more neutrophilic pathways. These combined results indicate that the impact of obesity induced by HFD in experimental asthma is partly determined by the type of allergen used to trigger allergic airway responses. HFD in the HDM model appears to modulate neutrophilic inflammation, which is a key feature found in some obese asthmatic patients. Thus, this model should be favoured over the other models.