Fig 2: MAT1A and ASMase mRNA levels from liver samples of patients with ASH and NASH. A-B, Liver samples from control subjects and patients with ASH and NASH were used to determine the mRNA of MAT1A and ASMase. C-E, Correlation between the mRNA of ASMase and MAT1A in the cohort of patients with ASH and NASH. Clinical characteristics of patients are shown in Supplementary Table 1. *p < 0.05 vs. control subjects.

Fig 3: Mat1a-/-/ASMase-/- double knockout mice are protected against CD diet induced NASH. A, ASMase activity and body weight and liver to body weight changes from Mat1a-/- and Mat1a-/-/ASMase-/- mice fed RD or CD diet for 7 days. B–C, H&E and oil red staining of liver samples from Mat1a-/- and Mat1a-/-/ASMase-/- mice fed RD or CD diet for 7 days. D, liver triglycerides levels from Mat1a-/- and Mat1a-/-/ASMase-/- mice fed RD or CD diet for 7 days. E, Sirius red staining of liver samples from Mat1a-/- and Mat1a-/-/ASMase-/- mice fed RD or CD diet for 7 days, with the percentage of stained areas being 2.8 ± 0.4; 3.1 ± 0.4; 13.6 ± 1.6 and 3.5 ± 0.4, respectively. F, Liver hydroxyproline levels from Mat1a-/- and Mat1a-/-/ASMase-/- mice fed RD or CD diet for 7 days. G, Col1a1 and Pdgfr mRNA levels of liver samples from Mat1a-/-/ASMase-/- mice fed RD or CD diet for 7 days. H, Il1b and Ccl2 mRNA levels of liver samples from Mat1a-/-/ASMase-/- mice fed RD or CD diet for 7 days. Results are mean ± SEM of N = 5–7 mice per group. *p < 0.05 Mat1a-/-/ASMase-/- mice vs. Mat1a-/- fed CD diet. . (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)

Fig 4: ASMase knockdown protects Mat1a-/- mice against alcohol induced liver disease. A, ASMase activity from Mat1a-/- mice fed acute-on-chronic alcohol with or without treatment with control SH and ASMSH adenovirus. B, serum ALT and AST of Mat1a-/- mice fed acute-on-chronic alcohol with or without treatment with control SH and ASMSH adenovirus. C-D, representative images of H&E and Oil red staining of liver sections. F, Sirius red staining for liver samples from Mat1a-/- mice fed acute-on-chronic alcohol with or without treatment with control SH and ASMSH adenovirus, with the percentage of stained areas being 2.4 ± 0.3; 12.1 ± 1.4 and 2.5 ± 0.3, respectively. F, serum ethanol levels of Mat1a-/- mice fed acute-on-chronic alcohol with or without treatment with control SH and ASMSH adenovirus. G, Hepatic hydroxyproline levels and Tfgb and Col1a1 mRNA levels of Mat1a-/- mice fed acute-on-chronic alcohol with or without treatment with control SH and ASMSH adenovirus. H, Tnfa, Ccl2 and Il6 mRNA levels from Mat1a-/- mice fed acute-on-chronic alcohol with or without treatment with control SH and ASMSH adenovirus. Results are mean ± SEM of N = 5–7 mice per group. *p < 0.05 vs. Mat1a-/- mice fed pair-fed diet or ethanol diet plus ASMSH treatment. . (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)

Fig 5: ASMase knockdown protects Mat1a-/- mice against CD diet induced NASH. A, ASMase activity in Mat1a-/- mice fed RD or CD diet for 14 days with or without treatment with control SH and ASMSH adenovirus. B, Body weight and liver to body weight change in Mat1a-/- mice fed RD or CD diet for 14 days with or without treatment with control SH and ASMSH adenovirus. C, serum ALT and AST in Mat1a-/- mice fed RD or CD diet for 14 days with or without treatment with control SH and ASMSH adenovirus. D, liver triglyceride content Mat1a-/- mice fed RD or CD diet for 14 days with or without treatment with control SH and ASMSH adenovirus. E-F, representative images of H&E, and oil red staining of liver sections. G Sirius red staining of liver samples from Mat1a-/- mice fed RD or CD diet for 14 days with or without treatment with control SH and ASMSH adenovirus, with the percentage of stained areas being 2.5 ± 0.3; 3.0 ± 0.4; 12.5 ± 1.7 and 2.8 ± 0.3, respectively. H, Liver hydroxyproline content and col1a1 and a-sma mRNA levels from Mat1a-/- mice fed RD or CD diet for 14 days with or without treatment with control SH and ASMSH adenovirus. I, Tnfa, Ccl2 and Il1b mRNA levels of Mat1a-/- mice fed RD or CD diet for 14 days with or without treatment with control SH and ASMSH adenovirus. Results are mean ± SEM of N = 5–7 mice per group. *p < 0.05 Mat1a-/- mice fed CD diet treated with control SH vs ASMSH treatment. . (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)