Increased diacylglycerols characterize hepatic lipid changes in progression of human nonalcoholic fatty liver disease; comparison to a murine model.
Increased diacylglycerols characterize hepatic lipid changes in progression of human nonalcoholic fatty liver disease; comparison to a murine model.
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DOI：
10.1371/journal.pone.0022775
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Brown HA
中科院分区：
文献类型：
--
作者：
Gorden DL;Ivanova PT;Myers DS;McIntyre JO;VanSaun MN;Wright JK;Matrisian LM;Brown HA
非酒精性脂肪性肝病（NAFLD）的范围包括脂肪变性、非酒精性脂肪性肝炎（NASH）和进展为肝硬化。虽然已经报道了不同疾病状态之间肝脏脂质的差异，但先前尚未描述脂质物质水平下磷脂和二酰基甘油（DAG）的精确组成。本研究的目的是通过使用先进的脂质组学技术描述人类NAFLD进展过程中脂质种类的变化，并将其与早期和晚期NAFLD的小鼠模型进行比较。利用质谱脂质组学，在正常和患病的人类和小鼠肝脏提取物中鉴定了超过250种磷脂和二酰甘油物质（DAG）。证明了正常和患病肝脏的磷脂组成之间的显著差异，特别是在DAG物种之间，与先前报道的DAG转移酶参与NAFLD和肝纤维化的进展一致。此外，在人胆汁性肝提取物中发现了一种新的磷脂物质（醚连接磷脂酰肌醇）。使用鼠和人肝脏组织的平行脂质组学分析，确定维持高脂肪饮食的小鼠提供了关于肝脏中脂质种类特异性的可再现的NAFLD模型。这些研究表明，新的脂质种类可以作为晚期肝病的标志物，重要的是，DAG种类的显著增加是NAFLD的标志。升高的DAG可能有助于改变疾病特征性的甘油三酯、磷脂酰胆碱（PC）和磷脂酰乙醇胺（PE）水平，并且特定DAG种类可能是NAFLD进展中重要的脂质信号传导分子。
The spectrum of nonalcoholic fatty liver disease (NAFLD) includes steatosis, nonalcoholic steatohepatitis (NASH), and progression to cirrhosis. While differences in liver lipids between disease states have been reported, precise composition of phospholipids and diacylglycerols (DAG) at a lipid species level has not been previously described. The goal of this study was to characterize changes in lipid species through progression of human NAFLD using advanced lipidomic technology and compare this with a murine model of early and advanced NAFLD. Utilizing mass spectrometry lipidomics, over 250 phospholipid and diacylglycerol species (DAGs) were identified in normal and diseased human and murine liver extracts. Significant differences between phospholipid composition of normal and diseased livers were demonstrated, notably among DAG species, consistent with previous reports that DAG transferases are involved in the progression of NAFLD and liver fibrosis. In addition, a novel phospholipid species (ether linked phosphatidylinositol) was identified in human cirrhotic liver extracts. Using parallel lipidomics analysis of murine and human liver tissues it was determined that mice maintained on a high-fat diet provide a reproducible model of NAFLD in regards to specificity of lipid species in the liver. These studies demonstrated that novel lipid species may serve as markers of advanced liver disease and importantly, marked increases in DAG species are a hallmark of NAFLD. Elevated DAGs may contribute to altered triglyceride, phosphatidylcholine (PC), and phosphatidylethanolamine (PE) levels characteristic of the disease and specific DAG species might be important lipid signaling molecules in the progression of NAFLD.
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影响因子：
2.9
作者：
Milne, Stephen B.;Ivanova, Pavlina T.;Armstrong, Michelle D.;Myers, David S.;Lubarda, Jovana;Shulga, Yulia V.;Topham, Matthew K.;Brown, H. Alex;Epand, Richard M.
通讯作者：
Epand, Richard M.
影响因子：
2.9
作者：
Rouzer, Carol A.;Ivanova, Pavlina T.;Marnett, Lawrence J.
通讯作者：
Marnett, Lawrence J.
影响因子：
6.5
作者：
Ivanova, Pavlina T.;Milne, Stephen B.;Brown, H. Alex
通讯作者：
Brown, H. Alex
影响因子：
13.5
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.
通讯作者：
Sanyal, Arun J.
影响因子：
4.8
作者：
Milne, Stephen;Ivanova, Pavlina;Brown, H. Alex
通讯作者：
Brown, H. Alex