Functional proteomic analysis of nonalcoholic fatty liver disease in rat models

作者：Xuequn Zhang, Juntao Yang, Yuanbiao Guo, Hua Ye, Chaohui Yu, Chengfu Xu, Lei Xu, Songfeng Wu, Wei Sun, Hangdong Wei, Xueqin Gao, Yunping Zhu, Xiaohong Qian, Ying Jiang, Youming Li, Fuchu He · 发表于：Hepatology · 年份：2009 · DOI：10.1002/hep.23486 · 被引用次数：85 · 研究领域：Liver Disease Diagnosis and Treatment、Metabolomics and Mass Spectrometry Studies、Fatty Acid Research and Health

UNLABELLED: Nonalcoholic fatty liver disease (NAFLD) has emerged as a common public health problem that can progress to end-stage liver disease. A high-fat diet (HFD) may promote the development of NAFLD through a mechanism that is poorly understood. We adopted a proteomic approach to examine the effect of HFD on the liver proteome during the progression of NAFLD. Male Sprague-Dawley rats fed an HFD for 4, 12, and 24 weeks replicated the progression of human NAFLD: steatosis, nonspecific inflammation, and steatohepatitis. Using two-dimensional difference gel electrophoresis (DIGE) combined with matrix-assisted laser desorption ionization time of flight/time of flight analysis, 95 proteins exhibiting significant changes (ratio > or = 1.5 or < or =-1.5, P < 0.05) during the development of NAFLD were identified. Biological functions for these proteins reflected phase-specific characteristics during the progression of the disease. The potential role of enoyl-coenzyme A hydratase (ECHS1), an enzyme that catalyzes the second step of mitochondrial fatty acid beta-oxidation, received further investigation. First, the reduced protein level of ECHS1 was validated both in rat models and in patients with biopsy-proven hepatic simple steatosis via immunoblotting or immunohistochemical analysis. Then the small interfering RNA (siRNA)-mediated knockdown of ECHS1 in the murine hepatocyte cell line alpha mouse liver 12 (AML12) demonstrated increased cellular lipid accumulation induced by free...