Integrated multiomics analysis reveals changes in liver physiological function in Aqp9 gene knockout mice

Aquaporin 9 (AQP9) is the main channel by which blood glycerol enters the liver, where it plays key roles in osmotic pressure regulation and energy metabolism. Previous studies have shown that AQP9 is involved in the pathogenesis of many liver diseases. In this study, we aimed to clarify the role of AQP9 in maintaining the physiological environment of the liver using Aqp9−/− mice. We constructed Aqp9 knockout mice and used comprehensive multiomics analysis to elucidate the potential molecular effects of AQP9 expression on liver tissue. Knockout of Aqp9 reduced mouse body weight by affecting glycerol metabolism and led to hepatocyte death and inflammatory cell infiltration, which was confirmed by transcriptomics, proteomics and metabolomics. Moreover, knockout of Aqp9 triggered immune and inflammatory responses, leading to scattered and mild liver cell pyroptosis and compensatory liver cell proliferation. •Knockout of Aqp9 recruits B cells and CD4+ T cells.•Knockout of Aqp9 can activate macrophages.•Knockout of Aqp9 can induce immune and inflammatory responses.•Knockout of Aqp9 leads to pyroptosis of hepatocytes.