原標(biāo)題：肥胖性哮喘患者的代謝轉(zhuǎn)換促進(jìn)C18：0神經(jīng)酰胺蓄積
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(huì)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(cè)定肥胖對(duì)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(guò)分析公共微陣列數(shù)據(jù)來(lái)研究鞘脂代謝變化與巨噬細(xì)胞極化的關(guān)系。此外，我們通過(guò)喂養(yǎng)高脂飼料的方式來(lái)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(xì)胞在極化過(guò)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(xì)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(dá)增加。
結(jié)論：鞘脂代謝改變會(huì)促進(jìn)神經(jīng)酰胺的蓄積（特別是長(zhǎng)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
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 
　　創(chuàng)建過(guò)敏性疾病的科研、科普知識(shí)交流平臺(tái)，為過(guò)敏患者提供專業(yè)診斷、治療、預(yù)防的共享平臺(tái)。