Plasma phospholipids and fatty acid composition differ between liver biopsy-proven nonalcoholic fatty liver disease and healthy subjects.
Plasma phospholipids and fatty acid composition differ between liver biopsy-proven nonalcoholic fatty liver disease and healthy subjects.
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DOI：
10.1038/nutd.2016.27
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发表时间：
2016-07-18
影响因子：
6.1
通讯作者：
Allard JP
中科院分区：
文献类型：
--
作者：
Ma DW;Arendt BM;Hillyer LM;Fung SK;McGilvray I;Guindi M;Allard JP
越来越多的证据表明非酒精性脂肪肝（NAFLD）与肝脏脂质代谢紊乱有关。肝脏磷脂和脂肪酸组成已被证明在 NAFLD 中发生改变。然而，缺乏 NAFLD 发病机制中循环脂质的详细概况。因此，本研究的目的是检查肝活检证实的单纯性脂肪变性（SS）、非酒精性脂肪性肝炎（NASH）和健康受试者之间的循环脂质和与肝基因表达相关的潜在机制。测定了 31 名健康活体肝脏捐献者（作为健康对照 (HC)）、26 名单纯性肝脂肪变性 (SS) 患者和 20 名进行性 NASH 患者的血浆磷脂和脂肪酸组成。通过 Illumina 微阵列分析了 22 名 HC、16 名 SS 和 14 名 NASH 患者的肝基因表达。磷脂酰乙醇胺（PE）浓度随疾病进展而增加，HC<SS<NASH（170<210<250μgml−1），并且HC和NASH之间存在显着差异（P<0.05）。 SS和NASH患者的循环磷脂酰丝氨酸（PS）和磷脂酰肌醇均高于HC（P<0.05），但SS和NASH之间无差异。磷脂的脂肪酸组成也被重塑。特别是，SS 和 NASH 中的二十二碳六烯酸和花生四烯酸相对于 PS 中的 HC 较高（P<0.05）。差异表达的肝脏基因包括分别参与PE合成和PS转运的ETNK1和PLSCR1。本研究表明，SS 中存在磷脂代谢紊乱，但 NASH 中更为明显。针对脂质代谢的干预研究可能有益于 SS 和 NASH。
There is growing evidence that nonalcoholic fatty liver disease (NAFLD) is associated with perturbations in liver lipid metabolism. Liver phospholipid and fatty acid composition have been shown to be altered in NAFLD. However, detailed profiles of circulating lipids in the pathogenesis of NAFLD are lacking. Therefore, the objective of the present study was to examine circulating lipids and potential mechanisms related to hepatic gene expression between liver biopsy-proven simple steatosis (SS), nonalcoholic steatohepatitis (NASH) and healthy subjects. Plasma phospholipid and fatty acid composition were determined in 31 healthy living liver donors as healthy controls (HC), 26 patients with simple hepatic steatosis (SS) and 20 with progressive NASH. Hepatic gene expression was analyzed by Illumina microarray in a subset of 22 HC, 16 SS and 14 NASH. Concentrations of phosphatidylethanolamine (PE) increased relative to disease progression, HC<SS<NASH (170<210<250 μg ml−1), and was significantly different (P<0.05) between HC and NASH. Circulating phosphatidylserine (PS) and phosphatidylinositol were higher in SS and NASH compared with HC (P<0.05), but there was no difference between SS and NASH. Fatty acid composition of phospholipids was also remodeled. In particular, docosahexaenoic and arachidonic acid were higher (P<0.05) in SS and NASH relative to HC in PS. Differentially expressed hepatic genes included ETNK1 and PLSCR1 that are involved in PE synthesis and PS transport, respectively. The present study demonstrates that there is a disruption in phospholipid metabolism that is present in SS, but more pronounced in NASH. Intervention studies targeted at lipid metabolism could benefit SS and NASH.