Extended Data Fig. 4: ACMSD inhibitors protect hepatic function from NAFLD induced by MCD diet.
From: De novo NAD+ synthesis enhances mitochondrial function and improves health
a, Plasma aspartate transaminase (AST) levels in 16-week-old C57BL/6J male mice fed for 2.5 weeks with control diet, MCD diet or MCD diet supplemented with 15mg kg−1 day−1 TES-991 (n = 8 mice). b, Representative photomicrographs of liver tissues stained with H&E or Oil red O from the mouse cohorts described in a. The experiment was performed twice independently. c, Representative photomicrographs of liver tissues from the mouse cohorts described in a, stained with CD45 and the corresponding negative control. The experiment was performed twice independently. d, Hepatic SOD2 activity in mouse cohorts described in a (chow diet, n = 8; MCD diet, n = 7; MCD diet + TES-991, n = 6 mice). e–h, Liver NAD+ (e), triglyceride content (f), plasma ALT (g) and AST (h) levels in congenic C57BL/6J Sirt1hep−/− mice that match the mouse cohorts described in a regarding age, gender and treatment duration (chow diet, n = 8; MCD diet, MCD diet + TES-991, n = 10 mice). i, Representative photomicrographs of liver tissues stained with H&E from the Sirt1hep−/− mice described in e–h. The experiment was performed once. j, Hepatic SOD2 activity in congenic C57BL/6J Sirt1hep−/− mice described in e–h (chow diet, n = 8; MCD diet, MCD diet + TES-991, n = 9 mice). k, mRNA levels of oxidative stress defence, mitochondrial, β-oxidation, inflammatory and fibrosis genes in livers of Sirt1hep−/− mice (n = 8 mice). Data are mean ± s.e.m. *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001. P values calculated using two-tailed t-test. For individual P values, see Source Data.
