Fig. 1.

Hepatocyte-specific OGT deletion leads to liver inflammation and moderate liver injury at 4 weeks.

Male liver-specific Ogt knockout mice (OGT^LKO) and control floxed littermates (OGT^LWT) were studied 4 weeks after birth in the fed state. (A) Fed blood glucose (mmol/L), body weight (g), liver weight, and spleen weight are shown. Liver and spleen weights are represented as percentage of body weight. (B) Relative Ogt expression normalised to TBP. (C) Relative Oga expression normalised to TBP. (D) Western blot analysis of OGT and O-GlcNAcylation levels in the liver, muscle, WAT, and BAT of OGT^LWT and OGT^LKO mice. Tubulin was used as a loading control. One representative sample is presented per condition. (E) Liver sections stained with H&E, Sirius Red, ɑSMA, Krt7, OGT, SOX9, and TUNEL. Scale bars = 100 μm. (F) Relative expression levels of fibrosis markers normalised to TBP. (G) Serum levels of ALT, AST, and LDH. (H) Relative expression levels of proliferation markers normalised to TBP. (I) Relative expression levels of inflammatory markers normalised to TBP. (J) Serum levels of Cxcl1. Data are shown as mean ± SEM of 5–10 individual male mice. ∗p <0.05, ∗∗p <0.01, ∗∗∗p <0.001 by unpaired Student’s t test (Mann–Whitney U test). ɑSMA, alpha-smooth muscle actin; ALT, alanine aminotransferase; AST, aspartate aminotransferase; BAT, brown adipose tissue; Ccl5, C–C motif chemokine ligand 5; Col3a1, collagen type III alpha 1 chain; Col6a1, collagen type VI alpha 1 chain; Cxcl1, C–X–C motif chemokine ligand 1; CycA2, cyclin A2; CycB1, cyclin B1; CycD1, cyclin D1; Krt7, cytokeratin 7; LDH, lactate dehydrogenase; Mcp1, monocyte chemoattractant protein-1; OGA, O-GlcNAcase; OGT, O-GlcNAc transferase; SOX9, sex determining region Y-box 2; TBP, TATA-box binding protein; TGFβ, transforming growth factor beta; Tnfɑ, tumour necrosis factor alpha; TUNEL, terminal deoxynucleotidyl transferase dUTP nick end labelling; WAT, white adipose tissue.