GPR35 agonist 7

C57BL/6 J (male, 8 weeks old, MASH induced by 60% fat high-fat diet for 16 weeks)^[1]

5 mg/kg; 10 mg/kg

i.p.; daily; 8 weeks

Reduced body weight relative to the HFD control, with the 10 mg/kg dose showing more significant reduction.
Significantly reduced liver weight compared to the HFD control.
Reduced lipid accumulation in liver sections (Oil Red O staining) in both groups, with the 10 mg/kg dose showing greater improvement.
Reversed HFD-induced elevations in serum triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), aspartate aminotransferase (AST), and alanine aminotransferase (ALT), and restored reduced high-density lipoprotein cholesterol (HDL-C) levels in a concentration-dependent manner.
Significantly reduced elevated hepatic TG and total cholesterol (T-CHO) levels relative to the HFD control.
Normalized HFD-induced upregulation of lipid synthesis genes (FASN, SREBP-1c, LXR, SCD1, ACC1, CHREBP, HMGCR) and CD36, while restoring downregulated fatty acid β-oxidation genes (PPARα, CPT1).
Upregulated PPAR-γ and AMPK mRNA expression to improve insulin sensitivity and energy metabolism regulation.
Reversed HFD-induced upregulation of lipid synthesis proteins (FASN, SREBP-1c, LXR, ACC1) and upregulated PPAR-α protein expression to enhance fatty acid β-oxidation.
Significantly reduced collagen surface area (Sirius Red staining) and decreased α-smooth muscle actin (α-SMA) mRNA and protein levels relative to the HFD control.
Reduced HFD-induced elevated hepatic malondialdehyde (MDA) levels and suppressed mRNA expression of inflammatory markers (TNF-α, ASC, caspase-1, IL-1β) relative to the HFD control.