ACLY-IN-3

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

10 mg/kg; 30 mg/kg

i.p.; daily; 8 weeks

Reduced average body weight from 49.5 g (HFD group) to 41.7 g (10 mg/kg) and 35.7 g (30 mg/kg).
Significantly lowered elevated serum triglycerides, total cholesterol, alanine aminotransferase, aspartate aminotransferase, and low-density lipoprotein cholesterol, while restoring reduced serum high-density lipoprotein cholesterol to near control levels.
Significantly reduced liver weight, hepatic triglycerides, and hepatic total cholesterol compared to the HFD group.
Achieved near-complete reversal of hepatic lipid accumulation (Oil Red O staining).
Significantly downregulated hepatic mRNA expression of lipogenic markers (FASN, LXR, SREBP-1c, HMGCR, ACC1) and fatty acid uptake marker CD36, while upregulating fatty acid oxidation markers (PPARα, CPT1, PPARγ) and lipid metabolism regulator AMPKα1; confirmed corresponding protein expression changes for FASN, ACC1, and PPARα.
Improved glucose tolerance (reduced OGTT AUC) and insulin sensitivity (reduced ITT AUC) compared to the HFD group.
Significantly reduced hepatic malondialdehyde levels (oxidative stress marker), downregulated mRNA expression of inflammatory markers (CD68, TNF-α, NLRP3, ASC) and pro-fibrotic marker α-SMA, and reduced collagen deposition (Sirius Red staining) in liver tissue.
Restored normal hepatocellular morphology (H&E staining) with no detectable pathological changes in heart, spleen, lung, or kidney tissue.