Crosstalk between iron metabolic disorder and lipid metabolic disorder in hepatocarcinogenesis

代谢紊乱，如铁超载和/或肝脏脂肪沉积，是丙型肝炎病毒(HCV)相关肝癌发生的众所周知的病理生理学特征之一。利用表达丙型肝炎病毒多聚蛋白的雄性转基因小鼠，在肝脏铁超载的情况下发生肝脏脂肪变性继而发生肝细胞癌，研究了肝脏铁超载促进肝脏脂肪变性发生的机制。肝铁水平与肝脏中甘油三酯浓度呈正相关。铁相关的氧化应激加重线粒体损伤，导致肉碱棕榈酰转移酶I的表达减少，并诱导未折叠蛋白反应，从而增加参与脂质合成的转录因子--固醇调节元件结合蛋白I的表达。

Metabolic disorders such as iron overload and/or fatty deposition in the liver are one of the well-known pathophysiological features in hepatitis C virus (HCV)-associated hepatocarcinogenesis. Using male transgenic mice expressing the HCV polyprotein which develop hepatic steatosis followed by hepatocellular carcinoma in the presence of hepatic iron overload, we investigated the mechanisms by which hepatic iron overload contributed to the development of hepatic steatosis. Hepatic iron levels were positively correlated with triglyceride concentrations in the liver. Iron-related oxidative stress aggravated mitochondrial injury leading to reduced expression of carnitine palmitoyl transferase I, and induced unfolded protein response which in turn increased the expression of sterol-regulatory element binding protein I, a transcription factor involved in lipid synthesis.