mitochondrial molecular pathophysiology of nonalcoholic fatty liver disease a proteomics approach.线粒体非酒精性脂肪肝病的分子病理生理学蛋白质组学方法文档.pdf

International Journal of Molecular Sciences Review Mitochondrial Molecular Pathophysiology of Nonalcoholic Fatty Liver Disease: A Proteomics Approach Natalia Nuño-Lámbarri 1,†, Varenka J. Barbero-Becerra 1,†, Misael Uribe 2 and Norberto C. Chávez-Tapia 1,2, * 1 Traslational Research Unit, Médica Sur Clinic Foundation, Mexico City 14050, Mexico; nnunol@.mx (N.N.-L.); vbarberob@.mx (V.J.B.-B.) 2 Obesity and Digestive Diseases Unit, Médica Sur Clinic Foundation, Mexico City 14050, Mexico; muribe@.mx * Correspondence: nchavezt@.mx; Tel.: +525-55-424-7200 (ext. 6850) † These authors contributed equally to this work. Academic Editor: Amedeo Lonardo Received: 23 December 2015; Accepted: 19 February 2016; Published: 15 March 2016 Abstract: Nonalcoholic fatty liver disease (NAFLD) is a chronic liver condition that can progress to nonalcoholic steatohepatitis, cirrhosis and cancer. It is considered an emerging health problem due to malnourishment or a high-fat diet (HFD) intake, which is observed worldwide. It is well known that the hepatocytes’ apoptosis phenomenon is one of the most important features of NAFLD. Thus, this review focuses on revealing, through a proteomics approach, the complex network of protein interactions that promote fibrosis, liver cell stress, and apoptosis. According to different types of in vitro and murine models, it has been found that oxidative/nitrative protein stress leads to mitochondrial dysfunction, which plays a major role in stimulating NAFLD damage. Human studies have revealed the importance of novel biomarkers, such as retinol-binding protein 4, lumican, transgelin 2 and hemoglobin, which have a significant role in the disease. The post-genome era has brought proteomics technology, which allows the determination of molecular pathogenesis in NAFLD. This has led to the search for biomarkers which improve early diagnosis and optimal treatm