Obesity-dependent metabolic signatures associated with nonalcoholic fatty liver disease progression.
Obesity-dependent metabolic signatures associated with nonalcoholic fatty liver disease progression.
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DOI：
10.1021/pr201223p
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发表时间：
2012-04-06
影响因子：
4.4
通讯作者：
Mato JM
中科院分区：
文献类型：
--
作者：
Barr J;Caballería J;Martínez-Arranz I;Domínguez-Díez A;Alonso C;Muntané J;Pérez-Cormenzana M;García-Monzón C;Mayo R;Martín-Duce A;Romero-Gómez M;Lo Iacono O;Tordjman J;Andrade RJ;Pérez-Carreras M;Le Marchand-Brustel Y;Tran A;Fernández-Escalante C;Arévalo E;García-Unzueta M;Clement K;Crespo J;Gual P;Gómez-Fleitas M;Martínez-Chantar ML;Castro A;Lu SC;Vázquez-Chantada M;Mato JM
我们对非酒精性脂肪性肝病（NAFLD）从单纯性脂肪变性发展为脂肪性肝炎（NASH）的机制的理解仍然非常有限。尽管越来越多的研究将这种疾病与血清代谢物水平的改变联系起来，但开发基于代谢组的NAFLD预测因子的障碍是缺乏来自活检证实的患者的大型队列数据，这些患者与肥胖等关键代谢特征相匹配。我们研究了467例肝组织学正常（n=90）或诊断为NAFLD（脂肪变性，n=246; NASH，n=131）的活检个体，随机分为估计组（所有患者的80%）和验证组（所有患者的20%）。采用超高效液相色谱-质谱联用（UPLC-MS）对540种血清代谢物变量进行定性测定。代谢特征依赖于患者的体重指数（BMI），这表明NAFLD的发病机制可能因个体的肥胖程度而异。使用基于NAFLD血清代谢谱的BMI分层多变量模型来分离患有和不患有NASH的患者。受试者工作特征曲线下面积在估计组中为0.87，在验证组中为0.85。对应于最大平均诊断准确度（0.82）的截止值（0.54）预测NASH，灵敏度为0.71，特异性为0.92（阴性/阳性预测值= 0.82/0.84）。目前的数据表明，BMI依赖性血清代谢谱可能能够可靠地区分NASH与脂肪变性患者，这对NASH生物标志物和治疗干预的潜在新靶点的开发具有重要意义。
Our understanding of the mechanisms by which nonalcoholic fatty liver disease (NAFLD) progresses from simple steatosis to steatohepatitis (NASH) is still very limited. Despite the growing number of studies linking the disease with altered serum metabolite levels, an obstacle to the development of metabolome-based NAFLD predictors has been the lack of large cohort data from biopsy-proven patients matched for key metabolic features such as obesity. We studied 467 biopsied individuals with normal liver histology (n=90) or diagnosed with NAFLD (steatosis, n=246; NASH, n=131), randomly divided into estimation (80% of all patients) and validation (20% of all patients) groups. Qualitative determinations of 540 serum metabolite variables were performed using ultra-performance liquid chromatography coupled to mass spectrometry (UPLC-MS). The metabolic profile was dependent on patient body-mass index (BMI), suggesting that the NAFLD pathogenesis mechanism may be quite different depending on an individual’s level of obesity. A BMI-stratified multivariate model based on the NAFLD serum metabolic profile was used to separate patients with and without NASH. The area under the receiver operating characteristic curve was 0.87 in the estimation and 0.85 in the validation group. The cutoff (0.54) corresponding to maximum average diagnostic accuracy (0.82) predicted NASH with a sensitivity of 0.71 and a specificity of 0.92 (negative/positive predictive values = 0.82/0.84). The present data, indicating that a BMI-dependent serum metabolic profile may be able to reliably distinguish NASH from steatosis patients, have significant implications for the development of NASH biomarkers and potential novel targets for therapeutic intervention.
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影响因子：
4.8
作者：
Fan, CY;Pan, J;Reddy, JK
通讯作者：
Reddy, JK
人类脂肪肝病：旧问题和新见解。
DOI：
10.1126/science.1204265
发表时间：
2011-06-24
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Cohen JC;Horton JD;Hobbs HH
通讯作者：
Hobbs HH
影响因子：
64.8
作者：
Fu, Suneng;Yang, Ling;Li, Ping;Hofmann, Oliver;Dicker, Lee;Hide, Winston;Lin, Xihong;Watkins, Steven M.;Ivanov, Alexander R.;Hotamisligil, Goekhan S.
通讯作者：
Hotamisligil, Goekhan S.
影响因子：
29.4
作者：
Matteoni, CA;Younossi, ZM;McCullough, AJ
通讯作者：
McCullough, AJ
影响因子：
13.5
作者：
Kleiner, DE;Brunt, EM;Sanyal, AJ
通讯作者：
Sanyal, AJ