Analysis of pathological roles of hypoxic responses in the regulation of organ metabolism in fatty liver diseases

在这项研究中，我们旨在阐明缺氧反应在过量酒精和高脂肪饮食引起的脂肪肝疾病的发生和进展中的作用。我们发现缺氧诱导因子1 （HIF1）是缺氧反应的主要调节因子，在小鼠酒精性和非酒精性脂肪肝中作为一种防止异常脂质积累的保护机制，而它在疾病后期促进肝纤维化。这些结果为通过靶向HIF1成功调控缺氧反应能够控制脂肪肝及其相关疾病如肝硬化、肝癌的发展提供了重要证据。

In this study, we aimed to elucidate roles of hypoxic responses in the development and progression of fatty liver diseases evoked by excessive alcohol and high-fat diets. We found that hypoxia inducible factor1 (HIF1), a master regulator of hypoxic responses, serves as a protective mechanism against aberrant lipid accumulation in both alcoholic and non-alcoholic fatty liver in mice, whereas it promotes liver fibrosis in the latter stage of the disease. These results provide an important evidence that successful regulations of hypoxic response by targeting HIF1 can control the development of fatty liver and its related diseases such as liver cirrhosis and cancer.