Liu Ying, Zheng Jing, Zhang Hong Ping, Zhang Xin, Wang Lei, Wood Lisa, Wang Gang
Pneumology Group, Department of Integrated Traditional Chinese and Western Medicine, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, China.
Pneumology Group, Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, China.
Allergy Asthma Immunol Res. 2018 Nov;10(6):628-647. doi: 10.4168/aair.2018.10.6.628.
Obesity is associated with metabolic dysregulation, but the underlying metabolic signatures involving clinical and inflammatory profiles of obese asthma are largely unexplored. We aimed at identifying the metabolic signatures of obese asthma.
Eligible subjects with obese (n = 11) and lean (n = 22) asthma underwent body composition and clinical assessment, sputum induction, and blood sampling. Sputum supernatant was assessed for interleukin (IL)-1β, -4, -5, -6, -13, and tumor necrosis factor (TNF)-α, and serum was detected for leptin, adiponectin and C-reactive protein. Untargeted gas chromatography time-of-flight mass spectrometry (GC-TOF-MS)-based metabolic profiles in sputum, serum and peripheral blood monocular cells (PBMCs) were analyzed by orthogonal projections to latent structures-discriminate analysis (OPLS-DA) and pathway topology enrichment analysis. The differential metabolites were further validated by correlation analysis with body composition, and clinical and inflammatory profiles.
Body composition, asthma control, and the levels of IL-1β, -4, -13, leptin and adiponectin in obese asthmatics were significantly different from those in lean asthmatics. OPLS-DA analysis revealed 28 differential metabolites that distinguished obese from lean asthmatic subjects. The validation analysis identified 18 potential metabolic signatures (11 in sputum, 4 in serum and 2 in PBMCs) of obese asthmatics. Pathway topology enrichment analysis revealed that cyanoamino acid metabolism, caffeine metabolism, alanine, aspartate and glutamate metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, pentose phosphate pathway in sputum, and glyoxylate and dicarboxylate metabolism, glycerolipid metabolism and pentose phosphate pathway in serum are suggested to be significant pathways related to obese asthma.
GC-TOF-MS-based metabolomics indicates obese asthma is characterized by a metabolic profile different from lean asthma. The potential metabolic signatures indicated novel immune-metabolic mechanisms in obese asthma with providing more phenotypic and therapeutic implications, which needs further replication and validation.
肥胖与代谢失调相关，但肥胖型哮喘涉及临床和炎症特征的潜在代谢特征在很大程度上尚未得到探索。我们旨在确定肥胖型哮喘的代谢特征。
符合条件的肥胖（n = 11）和瘦（n = 22）哮喘患者接受了身体成分和临床评估、痰液诱导及血液采样。对痰液上清液进行白细胞介素（IL）-1β、-4、-5、-6、-13和肿瘤坏死因子（TNF）-α的评估，并检测血清中的瘦素、脂联素和C反应蛋白。通过正交投影到潜在结构判别分析（OPLS-DA）和通路拓扑富集分析，对痰液、血清和外周血单核细胞（PBMCs）中基于非靶向气相色谱飞行时间质谱（GC-TOF-MS）的代谢谱进行分析。通过与身体成分、临床和炎症特征的相关性分析，进一步验证差异代谢物。
肥胖哮喘患者的身体成分、哮喘控制情况以及IL-1β、-4、-13、瘦素和脂联素水平与瘦哮喘患者显著不同。OPLS-DA分析揭示了28种区分肥胖和瘦哮喘患者的差异代谢物。验证分析确定了肥胖哮喘患者的18种潜在代谢特征（痰液中11种、血清中4种、PBMCs中2种）。通路拓扑富集分析表明，痰液中的氰基氨基酸代谢、咖啡因代谢、丙氨酸、天冬氨酸和谷氨酸代谢、苯丙氨酸、酪氨酸和色氨酸生物合成、磷酸戊糖途径，以及血清中的乙醛酸和二羧酸代谢、甘油脂质代谢和磷酸戊糖途径被认为是与肥胖型哮喘相关的重要途径。
基于GC-TOF-MS的代谢组学表明，肥胖型哮喘的特征是具有与瘦哮喘不同的代谢谱。潜在的代谢特征表明肥胖型哮喘存在新的免疫代谢机制，具有更多的表型和治疗意义，这需要进一步的重复和验证。
