GPR35 agonist 8

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

5 mg/kg; 10 mg/kg

i.p.; daily; 8 weeks

Reduced body weight and liver weight compared to high-fat diet control.
Reversed high-fat diet-induced elevations in serum triglycerides, total cholesterol, low-density lipoprotein cholesterol, aspartate aminotransferase, and alanine aminotransferase, and restored reduced high-density lipoprotein cholesterol levels in a concentration-dependent manner.
Significantly reduced hepatic triglycerides and total cholesterol levels.
Reduced hepatic lipid accumulation as shown by Oil Red O staining.
Downregulated lipid synthesis genes (FASN, SREBP-1c, LXR, SCD1, ACC1, CHREBP, HMGCR) and fatty acid uptake gene CD36, while upregulated fatty acid β-oxidation genes (PPARα, CPT1).
Upregulated PPAR-γ and activated the AMPK signaling pathway to improve insulin sensitivity.
Reduced hepatic collagen surface area as shown by Sirius Red staining, and significantly reduced mRNA/protein levels of the fibrosis biomarker α-SMA.
Lowered hepatic malondialdehyde levels (a marker of oxidative stress).
Suppressed mRNA expression of inflammatory markers (TNF-α, ASC, caspase-1, IL-1β).