Fig. 2

Knockout of PGAM5 improves HFHF-induced obesity and suppresses hepatic inflammation and fibrosis in mice. WT and GKO mice were fed with HFHF for 12 weeks (N = 12–15). a Body weight from week 1 to week 12. b, c Ratio of liver/body weights (b) and liver TG content (c). d, e Biochemical measurement of serum ALT, AST and ALP (d), lipids and glucose (e) in mice. f–g Representative H&E staining of liver sections (f) and evaluation of NAS (including scores of steatosis, inflammation and ballooning injury) (g) in mice. The black arrow indicates scattered inflammation and the blue one indicates ballooning and MDB of hepatocytes. Scale bars, 25 μm. h–j Representative staining of LY6G and F4/80, PSR staining and IHC stainings for α-SMA and COL1A1 in liver sections and their statistics of positive cells density or positive area (%). Scale bars, 50 μm. k Serum levels of pro-inflammatory cytokines (TNF-α, IL-1, IL-6, IL-10) in mice. l Hepatic mRNA expressions of pro-fibrotic genes in mice. m, n Relative hepatic protein levels of α-SMA, COL1A1 and COL3A1 measured byWestern blot. *p < 0.05, **p < 0.01 compared with the WT group. ns, no significance; NAS, NAFLD activity score; ALT, alanine aminotransferase; AST, aspartate aminotransferase; ALP, alkaline phosphatase; TG, triglyceride; TC, total cholesterol; HDL, high density lipoprotein; LDL, low density lipoprotein; MDB, Mallory-Denk body; PSR, picrosirius red; α-SMA (Acta2), α smooth muscle actin; COL, collagen; Mmp, matrix metalloproteases; Timp, tissue inhibitors of Mmps; WT, wild type; GKO, global knockout