Fig. 7: Hepatic overexpression of Mettl3 ameliorates MCD-induced NASH.

a A schematic representation of the Rosa26-STOP-METTL3 targeting vector and generation of liver-specific overexpression of Mettl3 mice. b Tissue extracts from control and Mettl3-HOE mice were immunoblotted with antibodies to Flag and β-actin, respectively. Lane 1 Control liver; lane 2 HOE liver; lane 3 HOE White adipose tissue; lane 4 HOE Skeletal muscle; lane 5 HOE Brown adipose tissue; lane 6 HOE Heart; lane 7 HOE Spleen; lane 8 HOE Kidney, lane 9 HOE Brain. c Serum ALT activities (control, n = 10; Mettl3-HOE, n = 7; P = 0.0024). d H&E staining of liver from control and Mettl3-HOE mice fed an MCD for 2 weeks. e Liver TAG levels (control, n = 10; Mettl3-HOE, n = 7; P = 0.0243). f TUNEL-positive cells (n = 6 for each group; P = 0.00003). g Sirius Red staining of livers from control and Mettl3-HOE mice fed an MCD for 2 weeks (n = 5 for each group). h Relative mRNA levels (control, n = 7–8; Mettl3-HOE, n = 7–8; collagen1A1, P = 0.0365; αSMA, P = 0.2169; Mmp9, P = 0.0011; Tgfb1, P = 0.0072). i The relative lipid uptake in control and Mettl3-HOE mice at 8 weeks old (control, n = 9; Mettl3-HOE, n = 11; P < 0.0001). j, k Cd36 and Ccl2 mRNA levels (control, n = 10; Mettl3-HOE, n = 7; Cd36, P = 0.0121; Ccl2, P = 0.0178). l CD36 and CCL2 protein levels were measured by immunoblotting, quantified by ImageJ and normalized to Tubulin (n = 3 for each group; CD36, P = 0.0101; CCL2, P = 0.0427). n was the number of biologically independent mice. The samples were derived from the same experiment and the blots were processed in parallel. Data represent the mean ± SEM. Significance was determined by unpaired two-tailed Student’s t test analysis. *P < 0.05. **P < 0.01. Source data are provided as a Source Data file.