Tessari P, Coracina A, Cosma A, Tiengo A
Department of Clinical and Experimental Medicine, Chair of Metabolism, University of Padua, Italy.
Nutr Metab Cardiovasc Dis. 2009 May;19(4):291-302. doi: 10.1016/j.numecd.2008.12.015. Epub 2009 Apr 8.
Non-alcoholic fatty liver disease (NAFLD) is an increasingly recognized pathology with a high prevalence and a possible evolution to its inflammatory counterpart (non-alcoholic steatohepatitis, or NASH). The pathophysiology of NAFLD and NASH has many links with the metabolic syndrome, sharing a causative factor in insulin resistance. According to a two-hit hypothesis, increased intrahepatic triglyceride accumulation (due to increased synthesis, decreased export, or both) is followed by a second step (or "hit"), which may lead to NASH. The latter likely involves oxidative stress, cytochrome P450 activation, lipid peroxidation, increased inflammatory cytokine production, activation of hepatic stellate cells and apoptosis. However, both "hits" may be caused by the same factors. The aim of this article is to overview the biochemical steps of fat regulation in the liver and the alterations occurring in the pathogenesis of NAFLD and NASH.
非酒精性脂肪性肝病（NAFLD）是一种日益受到认可的病理状况，其患病率较高，并且有可能演变为其炎症性对应物（非酒精性脂肪性肝炎，即NASH）。NAFLD和NASH的病理生理学与代谢综合征有许多联系，在胰岛素抵抗方面存在共同的致病因素。根据“二次打击”假说，肝内甘油三酯积累增加（由于合成增加、输出减少或两者兼有）之后会出现第二步（或“打击”），这可能导致NASH。后者可能涉及氧化应激、细胞色素P450激活、脂质过氧化、炎症细胞因子产生增加、肝星状细胞激活和细胞凋亡。然而，这两个“打击”可能由相同的因素引起。本文的目的是概述肝脏脂肪调节的生化步骤以及NAFLD和NASH发病机制中发生的改变。
