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In vitro, hepatocytes showed that the expression of HRG was upregulated under hypoxia/re-oxygenation conditions, but not in response to oleic acid treated hepatocytes. The decrease in HRG expression in fatty hepatocytes was accompanied by decreased Farnesoid X receptor (FXR) and Hypoxia-inducible factor-2α (HIF-2α) expression. HRG is a hepatoprotective factor during hepatic I/R injury by decreasing neutrophil infiltration and NETs formation. The decrease in HRG is a cause of susceptibility to I/R injury in steatotic livers. Therefore, H