# Protective role of fatty acid oxidation against epithelial barrier dysfunction in allergic asthma

## TL;DR

Fatty acid oxidation helps protect against asthma by maintaining lung cell barriers and reducing inflammation.

## Contribution

This study reveals that fatty acid oxidation protects against allergic asthma by preserving epithelial barrier function and reducing inflammation.

## Key findings

- FAO levels in lungs negatively correlate with inflammation and tissue injury in asthmatic mice.
- FAO regulates tight junction proteins and reduces epithelial barrier damage in bronchial cells.
- L-carnitine treatment alleviates asthma-related pathophysiology in both mice and cell models.

## Abstract

Fatty acid oxidation (FAO) is implicated in lung diseases, but its role in bronchial asthma is not fully understood. We investigated its effect on airway epithelial barrier integrity.

Using a house dust mite (HDM)-induced murine asthma model and HDM, IL-4, IL-13, or TNF-α stimulated human primary bronchial epithelial cells (BECs) and bronchial epithelial (Beas-2b) cells, we modulated FAO with L-carnitine (agonist) and Etomoxir (inhibitor). BECs and Beas-2b cells were infected with lentivirus-mediated CPT1A shRNA prior to stimulation. Barrier function, mitochondrial oxidative stress, inflammation, and metabolism were assessed.

FAO level in lungs negatively correlated with increased inflammation and tissue injury in HDM-induced asthmatic mice (all p < 0.05), while positively regulating tight junction protein expression. In BECs and Beas-2b cells, Etomoxir treatment and CPT1A knockdown exacerbated the impairment of FAO caused by various stimulants (all p < 0.05). Furthermore, FAO negatively regulated HDM/cytokine-induced epithelial barrier damage, hyperactive inflammatory response, and mitochondrial dysfunction in Beas-2b cells (all p < 0.05). In contrast, treatment with L-carnitine significantly alleviated these pathophysiological features in both in vivo and in vitro models.

FAO plays a protective role in the occurrence and development of asthma by maintaining airway epithelial cell homeostasis and barrier function.