Choi Youngwoo, Kim Minji, Kim Su Jung, Yoo Hyun-Ju, Kim Seung-Hyun, Park Hae-Sim
Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, South Korea.
Translational Research Laboratory for Inflammatory Disease, Clinical Trial Center, Ajou University Medical Center, Suwon, South Korea.
Allergy. 2020 Nov;75(11):2858-2866. doi: 10.1111/all.14366. Epub 2020 Sep 2.
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.
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/m , 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.
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.
Alteration in sphingolipid metabolism favoring ceramide accumulation (especially long-chain ceramides) may contribute to developing obese asthma.
与各种并发症相关的肥胖在全球范围内呈上升趋势。体重增加会改变脂质代谢产物（尤其是鞘脂），从而导致肥胖诱导的炎症。然而，这些代谢产物在肥胖性哮喘发展中的意义尚不清楚。
采用液相色谱 - 串联质谱法测定肥胖对照者（n = 7）和哮喘患者血清中鞘脂水平：肥胖组（BMI > 25 kg/m²，n = 13）与非肥胖组（n = 28）。为了研究鞘脂代谢变化与巨噬细胞极化之间的关系，分析了公开的微阵列数据。此外，对喂食高脂饮食的野生型BALB/c小鼠的鞘脂代谢变化进行了研究。
肥胖性哮喘患者血清中C18:0和C20:0神经酰胺水平高于非肥胖性哮喘组（分别为P = 0.028和P = 0.040）。血清C18:0神经酰胺（184.3 ng/mL）用于区分肥胖性哮喘和非肥胖性哮喘组的值显示出53.9%的敏感性和85.7%的特异性（AUC = 0.721，P = 0.024）。微阵列数据显示，在人类M1巨噬细胞极化过程中，神经酰胺合成显著增加，代谢转变为神经酰胺积累。肥胖小鼠出现气道高反应性增加、M1巨噬细胞极化和C18:0神经酰胺水平升高，但非肥胖小鼠未出现。在肥胖小鼠的肺组织中，神经酰胺合酶（CerS）1和CerS6（而非CerS2）的表达增加。
鞘脂代谢改变有利于神经酰胺积累（尤其是长链神经酰胺）可能有助于肥胖性哮喘的发展。
