Circulating phospholipid profiling identifies portal contribution to NASH signature in obesity
Circulating phospholipid profiling identifies portal contribution to NASH signature in obesity
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DOI：
10.1016/j.jhep.2014.11.002
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发表时间：
2015-04-01
影响因子：
25.7
通讯作者：
Tordjman, Joan
中科院分区：
文献类型：
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作者：
Anjani, Kavya;Lhomme, Marie;Tordjman, Joan
背景与目的：非酒精性脂肪性肝炎（NASH）的特点是脂肪变性、小叶炎症、肝细胞膨胀伴纤维化，严重者肥胖患病率高。我们旨在通过基于质谱的脂质组学分析来定义病态肥胖的 NASH 特征。方法：我们分析了减肥手术前和术后 12 个月的全身血液，以及手术时从肥胖女性收集的门静脉血和脂肪组织脂质流出物（9 个结构类别，150 个物种）。结果：几种甘油磷酸胆碱 (PC) 的浓度增加， 在 NASH 受试者的体循环中检测到甘油磷酸乙醇胺 (PE)、甘油磷酸肌醇 (PI)、甘油磷酸甘油 (PG)、溶血甘油磷酸胆碱 (LPC) 和神经酰胺 (Cer)。术后体重减轻（12 个月）改善了肝酶和多种脂质的水平，但大多数 PG 和 Cer 物种仍然升高。手术时肝门系统的脂质分析显示，与体循环相比，脂质变化有限，但发现 NASH 受试者的 PG 和 PE 类别显着增加。我们通过测量离体脂肪组织脂质流出来评估内脏脂肪组织对门静脉循环脂质变化的贡献，并且在 NASH 受试者中仅观察到微小的变化。有趣的是，临床和脂质组学数据（门静脉和全身）的整合使我们定义了 NASH 特征，其中脂质和临床参数具有同等贡献。结论：循环（门静脉和全身）磷脂谱和临床数据定义了病态肥胖的 NASH 特征。我们报告内脏脂肪组织对 NASH 相关门脉脂质改变的贡献较弱，这表明排入肝门脉系统的其他器官可能有贡献。 (C) 2015 年欧洲肝脏研究协会。由 Elsevier B.V. 出版。保留所有权利。
Background & Aims: Non-alcoholic steatohepatitis (NASH) is characterized by steatosis, lobular inflammation, hepatocyte ballooning with fibrosis in severe cases, and high prevalence in obesity. We aimed at defining NASH signature in morbid obesity by mass spectrometry-based lipidomic analysis.Methods: We analyzed systemic blood before and 12 months after bariatric surgery, along with portal blood and adipose tissue lipid efflux collected from obese women at the time of surgery (9 structural classes, 150 species).Results: Increased concentrations of several glycerophosphocholines (PC), glycerophosphoethanolamines (PE), glycerophosphoinositols (PI), glycerophosphoglycerols (PG), lyso-glycerophosphocholines (LPC), and ceramides (Cer) were detected in systemic circulation of NASH subjects. Post-surgery weight loss (12 months) improved the levels of liver enzymes, as well as several lipids, but most PG and Cer species remained elevated. Analysis of lipids from hepatic portal system at the time of surgery revealed limited lipid alterations compared to systemic circulation, but PG and PE classes were found significantly increased in NASH subjects. We evaluated the contribution of visceral adipose tissue to lipid alterations in portal circulation by measuring adipose tissue lipid efflux ex vivo, and observed only minor alterations in NASH subjects. Interestingly, integration of clinical and lipidomic data (portal and systemic) led us to define a NASH signature in which lipids and clinical parameters are equal contributors.Conclusions: Circulatory (portal and systemic) phospholipid profiling and clinical data defines NASH signature in morbid obesity. We report weak contribution of visceral adipose tissue to NASH-related portal lipid alterations, suggesting possible contribution from other organs draining into hepatic portal system. (C) 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.