Pathophysiological role of macrophages in development of NASH

非酒精性脂肪性肝炎(NASH)被认为是代谢综合征的一种肝脏表型，具有发展为肝硬变和肝细胞癌的高风险。分子机制仍不清楚，部分原因是没有合适的动物模型来反映类似于人类NASH的肝脏状况。在这项研究中，我们证明了高脂饮食的MC4R-KO小鼠将提供一种新的NASH小鼠模型，利用该模型可以研究饮食诱导的肝脏脂肪变性、肝纤维化和肝细胞癌等一系列事件。利用这一小鼠模型，我们发现在NASH发展过程中巨噬细胞的分布和功能发生了变化。

Non-alcoholic steatohepatitis(NASH) is considered a hepatic phenotype of metabolic syndrome and at high risk for the progression to cirrhosis and hepatocellular carcinoma. The molecular mechanisms are still unclear partly because of no appropriate animal models that reflect a liver condition similar to human NASH. In this study, we showed that MC4R-KO mice on a high-fat diet would provide a novel mouse model of NASH with which to investigate the sequence of events that comprise diet-induced hepatic steatosis, liver fibrosis, and hepatocellular carcinoma. Using this mouse model, we found changes in macrophage distribution and function during the course of NASH development.