Metabolic shift favoring C18:0 ceramide accumulation in obese asthma

• Published in: Allergy (Copenhagen) Vol. 75; no. 11; pp. 2858 - 2866
• Main Authors: Choi, Youngwoo, Kim, Minji, Kim, Su Jung, Yoo, Hyun‐Ju, Kim, Seung‐Hyun, Park, Hae‐Sim
• Format: Journal Article
• Language: English
• Published: Denmark Blackwell Publishing Ltd 01.11.2020
• Subjects: Animals; Asthma; Asthma - etiology; Body weight gain; Ceramide; Ceramides; High fat diet; Humans; Lipid metabolism; Liquid chromatography; macrophage; Macrophages; Mass spectroscopy; Metabolism; Metabolites; Mice; Mice, Inbred BALB C; Obesity; Obesity - complications; Polarization; Serum levels; sphingolipid; Sphingolipids; macrophage; ceramide; asthma; sphingolipid; obesity
• ISSN: 0105-4538; 1398-9995
• DOI: 10.1111/all.14366

Background 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. Methods 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 > 25 kg/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. Results 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 (184.3 ng/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. Conclusion Alteration in sphingolipid metabolism favoring ceramide accumulation (especially long‐chain ceramides) may contribute to developing obese asthma. This study evaluates the association between sphingolipid metabolism and development of obese‐related asthma phenotype. Serum C18:0 ceramide is increased in patients with obese asthma. Gene expression involved in macrophage polarization may be associated with ceramide accumulation. Abbreviations: CERK, ceramide kinase; CERS6, ceramide synthase 6; PPAP2A, phosphatidic acid phosphatase type 2A; PPAP2B, phosphatidic acid phosphatase type 2B; SGMS2, sphingomyelin synthase 2; UGCG, UDP‐glucose ceramide glucosyltransferase.