Plasma metabolomic profile in nonalcoholic fatty liver disease.
Plasma metabolomic profile in nonalcoholic fatty liver disease.
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DOI：
10.1016/j.metabol.2010.03.006
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发表时间：
2011-03
影响因子：
9.8
通讯作者：
Milburn, Mike
中科院分区：
文献类型：
--
作者：
Kalhan, Satish C.;Guo, Lining;Edmison, John;Dasarathy, Srinivasan;McCullough, Arthur J.;Hanson, Richard W.;Milburn, Mike
使用非针对性的整体代谢组学分析检查患有非酒精性脂肪肝病（NAFLD）、脂肪变性和脂肪性肝炎（NASH）受试者的血浆谱，以识别特定的疾病相关模式并识别潜在的非侵入性生物标志物。血浆样本是在禁食过夜后从经组织学证实患有肝脂肪变性 (N = 11) 或 NASH (N = 24) 的非糖尿病受试者中获得的，并与健康、年龄和性别匹配的对照 (n = 25) 进行比较。患有 NAFLD 的受试者肥胖、胰岛素抵抗，并且血浆同型半胱氨酸和总半胱氨酸浓度较高，而血浆总谷胱甘肽浓度较低。代谢组学分析显示，NAFLD 受试者的甘胆酸、牛磺胆酸和甘氨鹅脱氧胆酸水平显着升高。 NASH 患者血浆中长链脂肪酸浓度较低，游离肉碱、丁酰肉碱和甲基丁酰肉碱浓度较高。 NASH 和脂肪变性时，几种谷氨酰二肽水平较高，而半胱氨酸-谷胱甘肽水平较低。其他变化包括高级支链氨基酸、磷酸胆碱、碳水化合物（葡萄糖、甘露糖）、乳酸、丙酮酸和一些未知的代谢物。随机森林分析和代谢组数据的递归划分可以将健康受试者与 NAFLD 分开，错误率约为 8%，将 NASH 与健康对照分开，错误率为 4%。使用代谢组学谱无法区分肝脏脂肪变性和脂肪性肝炎。血浆代谢组学分析显示，非酒精性脂肪肝患者的胆汁盐和与谷胱甘肽相关的生化物质发生了显着变化。统计分析确定了一组生物标志物，可以有效区分健康对照与 NAFLD 以及健康对照与 NASH。这些生物标志物有可能用于追踪治疗干预的反应。
The plasma profile of subjects with non-alcoholic fatty liver disease (NAFLD), steatosis and steatohepatitis (NASH), was examined using an untargeted global metabolomic analysis in order to identify specific disease-related pattern/s and to identify potential non-invasive biomarkers. Plasma samples were obtained after an overnight fast from histologically confirmed non-diabetic subjects with hepatic steatosis (N=11) or NASH (N=24), and compared with healthy, age and sex-matched controls (n=25). Subjects with NAFLD were obese, were insulin resistant and had higher plasma concentration of homocysteine and total cysteine and lower plasma concentrations of total glutathione. Metabolomic analysis showed markedly higher levels of glycocholate, taurocholate and glycochenodeoxycholate in subjects with NAFLD. Plasma concentrations of long chain fatty acids were lower and concentrations of free carnitine, butyrylcarnitine and methylbutyryl carnitine were higher in NASH. Several glutamyl dipeptides were higher, while cysteine-glutathione levels were lower in NASH and steatosis. Other changes included higher branched chain amino acids, phosphocholine, carbohydrates (glucose, mannose), lactate, pyruvate, and several unknown metabolites. Random forest analysis and recursive partitioning of the metabolomic data could separate healthy subjects from NAFLD with an error rate of ~8%, and NASH from healthy controls with an error rate of 4%. Hepatic steatosis and steatohepatitis could not be separated using the metabolomic profile. Plasma metabolomic analysis revealed marked changes in bile salts and in biochemicals related to glutathione in subjects with non-alcoholic fatty liver disease. Statistical analysis identified a panel of biomarkers that could effectively separate healthy controls from NAFLD and healthy controls from NASH. These biomarkers can potentially be used to follow response to therapeutic interventions.
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DOI：
10.1016/s1570-0232(02)00401-4
发表时间：
2002-11-05
影响因子：
3
作者：
Garcia, AJ;Apitz-Castro, R
通讯作者：
Apitz-Castro, R
影响因子：
8.2
作者：
Marliss, EB;Chevalier, S;Wu, G
通讯作者：
Wu, G
DOI：
10.1016/0005-2760(78)90064-4
发表时间：
1978-01-01
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
NERVI, FO;SEVERIN, CH;VALDIVIESO, VD
通讯作者：
VALDIVIESO, VD
影响因子：
7.7
作者：
Darmaun, D;Smith, SD;Mauras, N
通讯作者：
Mauras, N
影响因子：
24.5
作者：
BOUCHIER, IAD;PENNINGTON, CR
通讯作者：
PENNINGTON, CR