ACLY-IN-4

C57BL/6J (male, 8 weeks old, 18-20 g, HFD-induced MASH)^[1]

10 mg/kg; 30 mg/kg

i.p.; daily; 8 weeks

Reduced average body weight to 46.0 g (10 mg/kg) and 32.9 g (vs 49.5 g in HFD control).
Significantly reduced serum triglyceride (TG), total cholesterol (T-CHO), alanine aminotransferase (ALT), aspartate aminotransferase (AST), low-density lipoprotein cholesterol (LDL-C), liver weight, hepatic TG, and hepatic T-CHO at 10 mg/kg.
Restored serum high-density lipoprotein cholesterol (HDL-C) levels at 10 mg/kg.
Significantly reduced hepatic lipid accumulation (confirmed by Oil Red O staining) at 10 mg/kg.
Suppressed hepatic mRNA expression of lipogenic markers (FASN, LXR, SREBP-1c, HMGCR, ACC1, CD36) and pro-inflammatory/fibrotic markers (CD68, TNF-α, NLRP3, ASC, α-SMA) at 10 mg/kg.
Restored mRNA expression of fatty acid oxidation markers (PPARα, CPT1, PPARγ, AMPKα1) at 10 mg/kg.
Reduced hepatic malondialdehyde (MDA) levels at 10 mg/kg.
Reduced liver protein levels of FASN, ACC1, NLRP3, ASC, α-SMA while increasing PPARα levels at 10 mg/kg.
Showed greater reductions in body weight, serum and hepatic lipid parameters, liver weight, and hepatic lipid accumulation than the 10 mg/kg dose at 30 mg/kg.
Produced similar significant effects on gene and protein expression of lipogenic, fatty acid oxidation, inflammatory, and fibrotic markers as the 10 mg/kg dose at 30 mg/kg.
Nearly restored hepatocellular morphology to match the standard diet control group (confirmed by H&E staining) at 30 mg/kg.