Britton Laurence J, Subramaniam V Nathan, Crawford Darrell Hg
Laurence J Britton, Darrell HG Crawford, Gallipoli Medical Research Institute, The University of Queensland, Greenslopes Private Hospital, Brisbane, Queensland 4120, Australia.
World J Gastroenterol. 2016 Sep 28;22(36):8112-22. doi: 10.3748/wjg.v22.i36.8112.
The mechanisms that promote liver injury in non-alcoholic fatty liver disease (NAFLD) are yet to be thoroughly elucidated. As such, effective treatment strategies are lacking and novel therapeutic targets are required. Iron has been widely implicated in the pathogenesis of NAFLD and represents a potential target for treatment. Relationships between serum ferritin concentration and NAFLD are noted in a majority of studies, although serum ferritin is an imprecise measure of iron loading. Numerous mechanisms for a pathogenic role of hepatic iron in NAFLD have been demonstrated in animal and cell culture models. However, the human data linking hepatic iron to liver injury in NAFLD is less clear, with seemingly conflicting evidence, supporting either an effect of iron in hepatocytes or within reticulo-endothelial cells. Adipose tissue has emerged as a key site at which iron may have a pathogenic role in NAFLD. Evidence for this comes indirectly from studies that have evaluated the role of adipose tissue iron with respect to insulin resistance. Adding further complexity, multiple strands of evidence support an effect of NAFLD itself on iron metabolism. In this review, we summarise the human and basic science data that has evaluated the role of iron in NAFLD pathogenesis.
非酒精性脂肪性肝病（NAFLD）中促进肝损伤的机制尚未完全阐明。因此，缺乏有效的治疗策略，需要新的治疗靶点。铁已被广泛认为与NAFLD的发病机制有关，是一个潜在的治疗靶点。大多数研究都指出了血清铁蛋白浓度与NAFLD之间的关系，尽管血清铁蛋白并不是衡量铁负荷的精确指标。在动物和细胞培养模型中，已经证明了肝脏铁在NAFLD发病机制中的多种致病作用机制。然而，将肝脏铁与NAFLD中的肝损伤联系起来的人体数据尚不清楚，证据似乎相互矛盾，既支持铁在肝细胞中的作用，也支持其在网状内皮细胞中的作用。脂肪组织已成为铁在NAFLD中可能具有致病作用的关键部位。这方面的证据间接来自评估脂肪组织铁对胰岛素抵抗作用的研究。更复杂的是，多条证据支持NAFLD本身对铁代谢的影响。在这篇综述中，我们总结了评估铁在NAFLD发病机制中作用的人体和基础科学数据。
