Fueling the Mechanisms of Asthma: Increased Fatty Acid Oxidation in Inflammatory Immune Cells May Represent a Novel Therapeutic Target

Abstract

Background

Increasing evidence has shown the close link between energy metabolism and the differentiation, function, and longevity of immune cells. Chronic inflammatory conditions such as parasitic infections and cancer trigger a metabolic reprogramming from the preferential use of glucose to the up-regulation of fatty acid oxidation (FAO) in myeloid cells, including macrophages and granulocytic and monocytic myeloid-derived suppressor cells. Asthma is another chronic inflammatory condition where macrophages, eosinophils, and polymorphonuclear cells play an important role in its pathophysiology.

Objective

We tested whether FAO might play a role in the development of asthma-like traits and whether the inhibition of this metabolic pathway could represent a novel therapeutic approach.

Methods

OVA and house dust mite (HDM)-induced murine asthma models were used in this study.

Results

Key FAO enzymes were significantly increased in the bronchial epithelium and inflammatory immune cells infiltrating the respiratory epithelium of mice exposed to OVA or HDM. Pharmacologic inhibition of FAO significantly decreased allergen-induced airway hyperresponsiveness, decreased the number of inflammatory cells, and reduced the production of cytokines and chemokines associated with asthma.

Conclusions and clinical relevance

These novel observations suggest that allergic airway inflammation increases FAO in inflammatory cells to support the production of cytokines, chemokines, and other factors important in the development of asthma. Inhibition of FAO may therefore provide a novel therapeutic approach for the treatment of asthma by re-purposing existing drugs that block FAO and are approved for the treatment of heart disease.

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