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

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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.