Background: House dust mites (HDM) can lead to the breakdown of the airway epithelial barrier, thus promote the development of asthma. Fatty acid oxidation (FAO) and its key rate-limiting enzyme carnitine lipoacyltransferase 1A (CPT1A) play an important role in regulating airway epithelial barrier function.

Aims and objectives?We assume that CPT1A and its regulated FAO maintain airway epithelial barrier function and further influence the progression of asthma.

Methods: 6-8 weeks C57 mice were randomly divided and inhaled CPT1A inhibitor Etomoxir, CPT1A shRNA or CPT1A agonist L-carnitine and HDM. The bronchoalveolar lavage fluid, blood serum and lungs were collected to test. Human primary bronchial epithelial cells and Beas-2b cells were pretreated with Etomoxir or L-carnitine or CPT1A shRNA, then stimulated with HDM/IL4/IL13/TNF-? separately. Rt-PCR, WB and TER were used to test the epithelial barrier, inflammation and mitochondrial damage. Seahorse XF96 and FAO metabolite related kit were used to test FAO.

Results: The present results showed that HDM leads to increased inflammation level, decreased CPT1A protein expression level in asthmatic mice. After Etomoxir treatment or CPT1A^-/-, the damages of asthmatic mice were further aggravated, while L-carnitine treatment reduced these damages.Compared with stimulated group, Etomoxir pretreatment or CPT1A^-/- further increased the damage, while L-carnitine pretreatment could partially offset the impact in cells. In CPT1A^-/- cells, the metabolism level is forced to less FAO level.

Conclusions: We examined CPT1A could reduce mitochondrial dysfunction by regulating the FAO of airway epithelial cells, thus maintaining the barrier function.