Altered Fatty Acid Metabolism and Reduced Stearoyl-Coenzyme A Desaturase Activity in Asthma

Abstract

Background

Fatty acids and lipid mediator signaling play an important role in the pathogenesis of asthma, yet this area remains largely under-explored. The aims of this study were (i) to examine fatty acid levels and their metabolism in obese and non-obese asthma patients and (ii) to determine the functional effects of altered fatty acid metabolism in experimental models.

Methods

Medium- and long-chain fatty acid levels were quantified in serum from 161 human volunteers by LC/MS. Changes in stearoyl-coenzyme A desaturase (SCD) expression and activity was evaluated in the ovalbumin (OVA) and house dust mite (HDM) murine models. Primary human bronchial epithelial cells from asthma patients and controls were evaluated for SCD expression and activity.

Results

The serum desaturation index (an indirect measure of SCD) was significantly reduced in non-obese asthma patients and in the OVA murine model. SCD1 gene expression was significantly reduced within the lungs following OVA or HDM challenge. Inhibition of SCD in mice promoted airway hyperresponsiveness. SCD1 expression was suppressed in bronchial epithelial cells from asthma patients. IL-4 and IL-13 reduced epithelial cell SCD1 expression. Inhibition of SCD reduced surfactant protein C expression and suppressed rhinovirus-induced IP-10 secretion, which was associated with increased viral titers.

Conclusions

This is the first study to demonstrate decreased fatty acid desaturase activity in humans with asthma. Experimental models in mice and human epithelial cells suggest that inhibition of desaturase activity leads to airway hyperresponsiveness and reduced anti-viral defense. SCD may represent a new target for therapeutic intervention in asthma patients.

This article is protected by copyright. All rights reserved.

http://ift.tt/2p0dmRg