The role of XBP1 in regulating the progression of non-alcoholic steatohepatitis [XWT/XKO BMDMs]

Our study demonstrated that XBP1 is upregulated in liver tissues of patients with NASH. Conditional knockout of Xbp1 in the hepatocytes resulted in decreased lipid accumulation in mice. Genetic specific deletion of Xbp1 in macrophages ameliorated nutritional steatohepatitis and fibrosis in mice by reducing the secretion of pro-inflammatory cytokine, increasing M2 macrophage polarization, and decreasing TGF-β1 expression. Pharmacological inhibition of XBP1 protects against steatohepatitis and fibrosis, highlighting a promising strategy for NASH therapy. LPS-primed Xbp1FL/FL（XWT）or Xbp1ΔMf（XKO）bone marrow-derived macrophages (BMDMs) were incubated with WT primary hepatocytes conditioned media (CM) for 48 h, and then Xbp1FL/FL or Xbp1ΔMf BMDMs were subjected to RNA sequencing analysis (n = 3/group).