The plasma lipidomic signature of nonalcoholic steatohepatitis.
The plasma lipidomic signature of nonalcoholic steatohepatitis.
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DOI：
10.1002/hep.23229
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发表时间：
2009-12
期刊：
影响因子：
13.5
通讯作者：
Sanyal, Arun J.
中科院分区：
文献类型：
--
作者：
Puri, Puneet;Wiest, Michelle M.;Cheung, Onpan;Mirshahi, Faridoddin;Sargeant, Carol;Min, Hae-Ki;Contos, Melissa J.;Sterling, Richard K.;Fuchs, Michael;Zhou, Huiping;Watkins, Steven M.;Sanyal, Arun J.
肝脏脂质组成的特定改变表征了非酒精性脂肪性肝病（NAFLD）的谱，其从非酒精性脂肪肝（NAFL）扩展到非酒精性脂肪性肝炎（NASH）。然而，NAFLD的血浆脂质组以及NASH是否具有独特的血浆脂质组学特征尚不清楚。在NAFL（n = 25）和NASH（n = 50）受试者中进行通过质谱法定量的血浆脂质和类花生酸代谢物的综合分析，并与瘦的正常对照（n = 50）进行比较。关键发现包括由棕榈油酸（16：1 n7）和油酸（18：1 n9）含量驱动的显著增加的总血浆单不饱和脂肪酸（对于NAFL和NASH中的两种酸，P < 0.01）。棕榈油酸、油酸和棕榈油酸与棕榈酸（16：0）的比例在多种脂质类别的NAFLD中显著增加。在NAFL和NASH中，亚油酸（8：2n 6）减少（P < 0.05），同时γ-亚麻酸（18：3 n6）和二高γ-亚麻酸（20：3 n6）增加（对于大多数脂质类别，P < 0.001）。在磷脂酰胆碱（PC）和磷脂酰乙醇胺（PE）池中，二十二碳己酸（22：6 n3）与二十二碳五烯酸（22：5 n3）的比率显著降低，这在NASH受试者中最显著（PC P < 0.01，PE P < 0.001）。NASH患者血浆总缩醛胺水平明显低于对照组（P < 0.05）。脂氧合酶（LOX）代谢物5（S）-羟基二十碳四烯酸（5-HETE）、8-HETE和15-HETE的逐步增加表征了从正常到NAFL到NASH的进展。11-HETE（花生四烯酸（20：4）的非酶氧化产物）的水平仅在NASH中显著增加。结论：尽管脂肪生成、去饱和酶和LOX活性增加表征了NAFL和NASH，但过氧化物酶体多不饱和脂肪酸（PUFA）代谢受损和非酶促氧化与NASH进展相关。
Specific alterations in hepatic lipid composition characterize the spectrum of nonalcoholic fatty liver disease (NAFLD), which extends from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH). However, the plasma lipidome of NAFLD and whether NASH has a distinct plasma lipidomic signature are unknown. A comprehensive analysis of plasma lipids and eicosanoid metabolites quantified by mass spectrometry was performed in NAFL (n = 25) and NASH (n = 50) subjects and compared with lean normal controls (n = 50). The key findings include significantly increased total plasma monounsaturated fatty acids driven by palmitoleic (16:1 n7) and oleic (18:1 n9) acids content (P < 0.01 for both acids in both NAFL and NASH). The levels of palmitoleic acid, oleic acid, and palmitoleic acid to palmitic acid (16:0) ratio were significantly increased in NAFLD across multiple lipid classes. Linoleic acid (8:2n6) was decreased (P < 0.05), with a concomitant increase in γ-linolenic (18:3n6) and dihomo γ-linolenic (20:3n6) acids in both NAFL and NASH (P < 0.001 for most lipid classes). The docosahexanoic acid (22:6 n3) to docosapentenoic acid (22:5n3) ratio was significantly decreased within phosphatidylcholine (PC), and phosphatidylethanolamine (PE) pools, which was most marked in NASH subjects (P < 0.01 for PC and P < 0.001 for PE). The total plasmalogen levels were significantly decreased in NASH compared with controls (P < 0.05). A stepwise increase in lipoxygenase (LOX) metabolites 5(S)-hydroxyeicosatetraenoic acid (5-HETE), 8-HETE, and 15-HETE characterized progression from normal to NAFL to NASH. The level of 11-HETE, a nonenzymatic oxidation product of arachidonic (20:4) acid, was significantly increased in NASH only. Conclusions: Although increased lipogenesis, desaturases, and LOX activities characterize NAFL and NASH, impaired peroxisomal polyunsaturated fatty acid (PUFA) metabolism and nonenzymatic oxidation is associated with progression to NASH.
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影响因子：
64.5
作者：
Cao H;Gerhold K;Mayers JR;Wiest MM;Watkins SM;Hotamisligil GS
通讯作者：
Hotamisligil GS
影响因子：
13.5
作者：
Browning, JD;Szczepaniak, LS;Hobbs, HH
通讯作者：
Hobbs, HH
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6
作者：
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Poniachik, J
影响因子：
13.5
作者：
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通讯作者：
Gores, GJ
影响因子：
13.5
作者：
Li, ZhengZheng;Berk, Michael;Feldstein, Ariel E.
通讯作者：
Feldstein, Ariel E.