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原标题：肥胖性哮喘患者的代谢转换促进C18：0神经酰胺蓄积
背景：与各种并发症相关的肥胖症在全世界范围内都在增加。体重增加会改变脂质代谢产物（尤其是鞘脂），从而导致肥胖引起的炎症。但是，脂质代谢物在肥胖性哮喘发展中的重要性尚不清楚。
方法：采用液相色谱-串联质谱法测定肥胖对照组（n=7）、肥胖型哮喘患者（BMI>25kg/m3，n=13）和非肥胖型哮喘患者组（n=28）的血清鞘脂水平。我们通过分析公共微阵列数据来研究鞘脂代谢变化与巨噬细胞极化的关系。此外，我们通过喂养高脂饲料的方式来研究野生型BALB/c小鼠体内鞘脂代谢的变化。
结果：肥胖型哮喘患者的血清C18：0和C20：0神经酰胺水平高于非肥胖型哮喘患者（分别为P = .028和P = .040）。血清C18：0神经酰胺（184.3 ng / mL）值可用于区分肥胖型哮喘与非肥胖型哮喘组，灵敏度为53.9%，特异性为85.7%（AUC = 0.721，P = .024）。微阵列数据显示，人M1巨噬细胞在极化过程中，神经酰胺的合成显著增加，代谢转变为神经酰胺蓄积。相较于正常小鼠，肥胖小鼠的气道高反应性、M1-巨噬细胞极化和C18:0神经酰胺水平增加。在肥胖小鼠的肺组织中，神经酰胺合成酶（CerS）1和CerS6（而不是CerS2）的表达增加。
结论：鞘脂代谢改变会促进神经酰胺的蓄积（特别是长链神经酰胺），这可能导致肥胖性哮喘的发生。


延伸阅读
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 
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