Metabolic shift favoring C18:0 ceramide accumulation in obese asthma.

Abstract

Obesity associated with various complications has increased worldwide. Body weight gain alters lipid metabolites (especially sphingolipids) contributing to obesity-induced inflammation. However, the significance of the metabolites in the development of obese asthma is not yet clear. The serum levels of sphingolipids were measured using liquid chromatography-tandem mass spectrometry in obese controls (n=7) and patients with asthma: the obese group (BMI>25kg/m2 , n=13) vs the nonobese (n=28) group. To examine the relationship between metabolic changes in sphingolipids and macrophage polarization, public microarray data were analyzed. In addition, the alteration in sphingolipid metabolism was investigated in wild-type BALB/c mice fed a high-fat diet. The obese asthma had higher levels of serum C18:0 and C20:0 ceramides than the nonobese asthma group (P=.028 and P=.040, respectively). The value of the serum C18:0 ceramide (184.3ng/mL) for discriminating the obese asthma from the nonobese asthma group showed 53.9% sensitivity and 85.7% specificity (AUC=0.721, P=.024). The microarray data showed significantly increased ceramide synthesis and metabolic shift to ceramide accumulation during M1 macrophage polarization in humans. Increased airway hyperresponsiveness, M1 macrophage polarization, and C18:0 ceramide levels were noted in obese mice, but not in nonobese mice. Increased expression of ceramide synthase (CerS) 1 and CerS6 (not CerS2) was noted in lung tissues of obese mice. Alteration in sphingolipid metabolism favoring ceramide accumulation (especially long-chain ceramides) may contribute to developing obese asthma.