Fig. 4: CPTH2 ameliorates mice from diet-induced MASLD and reduces PAOA-induced lipid accumulation in hepatocytes.

A–G Male C57BL/6 J mice at 8 weeks of age were randomly grouped. Mice were fed an HFD for 4 weeks, and then vehicle or CPTH2 (20 mg/kg/day) was administrated to mice by gastric irrigation daily. After 6 weeks of treatment, the mice were sacrificed and subjected to a series of analyses as indicated below. A Schematic diagram of HFD diet-induced MASLD models treated with CPTH2. B The protein levels of GCN5 and PCAF in the liver were verified by western blot (n = 3 independent mice). C LW, and LW/BW (n = 5 independent mice). D Oil red O staining and histological analysis of the liver (n = 5 independent mice). Scale bar: 50 μm. E The serum TG, TC, HDL-c, and LDL-c levels (n = 5 independent mice). F The liver TG and TC levels (n = 5 independent mice). G The serum AST, and ALT levels (n = 5 independent mice). H–N Male C57BL/6 J mice at 8 weeks of age were randomly grouped. Mice were fed the FPC diet for 16 weeks, and then vehicle or CPTH2 (20 mg/kg/day) was administrated to mice by gastric irrigation daily. After 6 weeks of treatment, the mice were sacrificed and subjected to a series of analyses as indicated below. H Schematic diagram of FPC diet-induced MASLD models treated with CPTH2. I The protein levels of GCN5 and PCAF in the liver were verified by western blot (n = 3 independent mice). J LW, and LW/BW (n = 6 independent mice). K Oil red O staining and histological analysis of the liver (n = 6 independent mice). Scale bar: 50 μm. L The serum TG, TC, HDL-c, and LDL-c levels (n = 6 independent mice). M The liver TG and TC levels (n = 6 independent mice). N The serum AST, and ALT levels (n = 6 independent mice). O–Q KAT2A KO cells were transfected with indicated plasmids for 12 h, incubated with PAOA with CPTH2 (50 μM) for 24 h, then stained with Nile Red and Bodipy (O), scale bar: 20 μm. Quantification of the cellular lipids was analyzed by ImageJ (P) (n = 6 independent cultures). The cellular TG and TC levels (Q) (n = 3 independent cultures). Error bars are represented as mean ± SEM. Statistical analysis was done using the two-tailed Student’s t test (C–G, J–N) and one-way ANOVA with Dunnett’s post-test (P–Q). Exact p-values are indicated in the figure. Source data are provided as a Source Data file.