Sodium butyrate activates peroxisome proliferator-activated receptor γ to suppress lithogenic diet-induced cholesterol gallstones in mice

Peroxisome proliferator-activated receptor γ (PPAR-γ) is crucial in forming cholesterol stones. Sodium butyrate (NaB), a short-chain fatty acid, shows potential for gallstone treatment by activating PPAR-γ. This study aimed to elucidate the effects of NaB on cholesterol gallstones in mice fed a lithogenic diet (LD). Ezetimibe (5 mg/day) was used as a positive control, and a PPAR-γ antagonist (CW9661, 4 mg/kg/day) was used to investigate PPAR-γ. Body weight, gallstone incidence, lipid concentrations in blood, bile, and liver, liver function evaluation, histological analysis, and cholesterol metabolism-related gene expression were evaluated. NaB and ezetimibe suppressed gallstone formation, serum AST, ALT, and ALP levels, and serum/liver TG and TC. They also reduced bile cholesterol and phospholipids, and liver histological damage. NaB activated PPAR-γ, CYP7A1, ABCA1, and ABCB11 while suppressing ABCG5/G8 gene expression. CW9661 reversed NaB’s benefits in LD mice. This study provides scientific evidence that NaB activated PPAR-γ to improve gallstones.