原標(biāo)題:肥胖性哮喘患者的代謝轉(zhuǎn)換促進C18:0神經(jīng)酰胺蓄積
——浙大迪迅 譯
背景:與各種并發(fā)癥相關(guān)的肥胖癥在全世界范圍內(nèi)都在增加。體重增加會改變脂質(zhì)代謝產(chǎn)物(尤其是鞘脂),從而導(dǎo)致肥胖引起的炎癥。但是,脂質(zhì)代謝物在肥胖性哮喘發(fā)展中的重要性尚不清楚。
方法:采用液相色譜-串聯(lián)質(zhì)譜法測定肥胖對照組(n=7)、肥胖型哮喘患者(BMI>25kg/m3,n=13)和非肥胖型哮喘患者組(n=28)的血清鞘脂水平。我們通過分析公共微陣列數(shù)據(jù)來研究鞘脂代謝變化與巨噬細胞極化的關(guān)系。此外,我們通過喂養(yǎng)高脂飼料的方式來研究野生型BALB/c小鼠體內(nèi)鞘脂代謝的變化。
結(jié)果:肥胖型哮喘患者的血清C18:0和C20:0神經(jīng)酰胺水平高于非肥胖型哮喘患者(分別為P = .028和P = .040)。血清C18:0神經(jīng)酰胺(184.3 ng / mL)值可用于區(qū)分肥胖型哮喘與非肥胖型哮喘組,靈敏度為53.9%,特異性為85.7%(AUC = 0.721,P = .024)。微陣列數(shù)據(jù)顯示,人M1巨噬細胞在極化過程中,神經(jīng)酰胺的合成顯著增加,代謝轉(zhuǎn)變?yōu)樯窠?jīng)酰胺蓄積。相較于正常小鼠,肥胖小鼠的氣道高反應(yīng)性、M1-巨噬細胞極化和C18:0神經(jīng)酰胺水平增加。在肥胖小鼠的肺組織中,神經(jīng)酰胺合成酶(CerS)1和CerS6(而不是CerS2)的表達增加。
結(jié)論:鞘脂代謝改變會促進神經(jīng)酰胺的蓄積(特別是長鏈神經(jīng)酰胺),這可能導(dǎo)致肥胖性哮喘的發(fā)生。
延伸閱讀
Allergy
[IF:6.771]
Metabolic shift favoring C18:0 ceramide accumulation in obese asthma
DOI: 10.1111/ALL.14366
Abstract:
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/m3, n = 13) vs the non-obese (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 non-obese 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 non-obese 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.
First Author:
Youngwoo Choi
Correspondence:
Translational Research Laboratory for Inflammatory Disease, Clinical Trial Center, Ajou University Medical Center, Suwon, South Korea.
All Authors:
Youngwoo Choi, Minji Kim, Su Jung Kim, Hyun-Ju Yoo, Seung-Hyun Kim, Hae-Sim Park
2020-11-10 Article
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