The metabolomic window into hepatobiliary disease.
The metabolomic window into hepatobiliary disease.
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DOI：
10.1016/j.jhep.2013.05.030
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发表时间：
2013-10
影响因子：
25.7
通讯作者：
Idle, Jeffrey R.
中科院分区：
文献类型：
--
作者：
Beyoglu, Diren;Idle, Jeffrey R.
关键词：
代谢组学这门新兴学科吸引了肝病学的大量研究努力。本文综述了非酒精性脂肪性肝病（NAFLD）、非酒精性脂肪性肝炎（NASH）、肝硬化、肝细胞癌（HCC）、胆管癌（CCA）、酒精性肝病（ALD）、B和C型肝炎、胆囊炎、胆汁淤积、肝移植和急性肝毒性动物模型的代谢组学数据。代谢组学窗口允许观察健康肝脏和肝细胞癌或胆管癌之间过渡阶段发生的生物化学变化。无论是由肥胖和糖尿病，酒精使用或致癌病毒引起，肝脏都会产生核心代谢组学表型（CMP），涉及胆汁酸和磷脂稳态的失调。CMP开始于健康肝脏（0期）和NAFLD/NASH、ALD或病毒性肝炎（1期）之间的过渡。这种CMP在存在或不存在肝硬化（2期）以及是否发生HCC或CCA（3期）的情况下保持不变。肝脏中的炎症信号触发CMP的出现。许多其他代谢组学标志物区分0、1、2和3期。已经描述了HCC中的代谢重塑，但所有四个阶段的代谢组学数据表明，从线粒体呼吸到胞质糖酵解的瓦尔堡转变预示着HCC，并且可能早在第1阶段就发生。代谢重塑还涉及脂肪酸β-氧化的上调，也从第1阶段开始。脂肪肝中甘油三酯的储存为肝脏病理学的2期和3期提供了高能量产生底物。肝胆疾病的代谢组学窗口为肝脏的系统病理学提供了新的线索。
The emergent discipline of metabolomics has attracted considerable research effort in hepatology. Here we review the metabolomic data for nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), cirrhosis, hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), alcoholic liver disease (ALD), hepatitis B and C, cholecystitis, cholestasis, liver transplantation and acute hepatotoxicity in animal models. A metabolomic window has permitted a view into the changing biochemistry occurring in the transitional phases between a healthy liver and hepatocellular carcinoma or cholangiocarcinoma. Whether provoked by obesity and diabetes, alcohol use or oncogenic viruses, the liver develops a core metabolomic phenotype (CMP) that involves dysregulation of bile acid and phospholipid homeostasis. The CMP commences at the transition between the healthy liver (Phase 0) and NAFLD/NASH, ALD or viral hepatitis (Phase 1). This CMP is maintained in the presence or absence of cirrhosis (Phase 2) and whether or not either HCC or CCA (Phase 3) develop. Inflammatory signalling in the liver triggers the appearance of the CMP. Many other metabolomic markers distinguish between Phases 0, 1, 2 and 3. A metabolic remodelling in HCC has been described but metabolomic data from all four Phases demonstrate that the Warburg shift from mitochondrial respiration to cytosolic glycolysis foreshadows HCC and may occur as early as Phase 1. The metabolic remodelling also involves an upregulation of fatty acid β-oxidation, also beginning in Phase 1. The storage of triglycerides in fatty liver provides high energy-yielding substrates for Phases 2 and 3 of liver pathology. The metabolomic window into hepatobiliary disease sheds new light on the systems pathology of the liver.
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影响因子：
4.1
作者：
Chen, Chi;Krausz, Kristopher W.;Shah, Yatrik M.;Idle, Jeffrey R.;Gonzalez, Frank J.
通讯作者：
Gonzalez, Frank J.
影响因子：
6.5
作者：
Cho, Joo-Youn;Matsubara, Tsutomu;Gonzalez, Frank J.
通讯作者：
Gonzalez, Frank J.
影响因子：
4.4
作者：
Craig, Andrew;Sidaway, James;Nicholson, Jeremy
通讯作者：
Nicholson, Jeremy
影响因子：
13.5
作者：
Beyoglu, Diren;Imbeaud, Sandrine;Maurhofer, Olivier;Bioulac-Sage, Paulette;Zucman-Rossi, Jessica;Dufour, Jean-Francois;Idle, Jeffrey R.
通讯作者：
Idle, Jeffrey R.
影响因子：
2
作者：
Aoki, Masayo;Konya, Yutaka;Komuro, Setsuko
通讯作者：
Komuro, Setsuko