Oxygen therapy alleviates hepatic steatosis by inhibiting hypoxia-inducible factor-2α.

Non-alcoholic fatty liver disease (NAFLD) is difficult to manage due to the lack of effective treatments. Increased oxygen consumption caused by ove rnutrition, along with reduced oxygen delivery to liver cells induces hepatic steatosi s. Here, we investigated the efficacy of oxygen therapy (OT) to alleviate hepatic steatosi s. The effect of OT on hepatic steatosis was evaluated in high-fat-diet (HFD)-fed mice and palmitic acid (PA)- treated primary hepatocytes. Liver biopsy tissue samples were u sed to determine the relationship between the expression of hypoxia-inducible fa ctor-2α (HIF-2α) and the progression of NAFLD. The role of HIF-2α in the OT group was determined based on the overexpression of HIF-2α in vitro. OT safely alleviated hepatic hypoxia and improved hepatic steatosis by inhibiting hepatic de novo lipogenesis in HFD-fed mice and PA-treated primary hepatocytes, and this was accompanied by red uced expression of HIF-2α and hepatic de novo lipogenesis. The analysis of liver tissues from individuals wi th or without NAFLD revealed a positive correlation between hepati c HIF-2α expression and NAFLD progression. Overexpression of HIF-2α in vitro inhibited the beneficial effect of OT against hepatic lipogenesis and steatosis. OT might be a via ble treatment option for NAFLD and functions by alleviating hypoxia and inhibiting the l iver HIF-2α signaling pathway. [ABSTRACT FROM AUTHOR]