Abstract: Objective To further investigate the relationship between leptin and bile acid metabolism. Methods Liver tissues and preoperative serum of 89 patients with Gall Stone (GS), 68 patients with Primary intrahepatic Stone (PIS) and 72 patients with benign liver diseases (Control, CT) were collected. Serum leptin levels were measured by radioimmunoassay, and the serum TBA, TBIL, ALT, AST, TC, TG and gamma-ggt levels were detected by automatic biochemical analysis. mRNA and protein expression levels of Adenosine monophosphate-activated protein kinase-a2, p-AMPKa2 and bile salt export pump (BSEP) in liver samples were measured by Q-PCR and Western blot, respectively. After co-culture of HepG2 cells with leptin and leptin+AMPKa2 inhibitor (compund C), mRNA and protein expressions of OB-Rb, AMPKa2, p-AMPKa2 and BSEP were detected by Q-PCR and Western blot, respectively. TBA content in cell supernatant was detected by automatic biochemical analysis. Results serum leptin level in GS group was significantly higher than that in CT and PIS group (P < 0.05). The expression levels of OB-Rb, AMPKa2, p-AMPKa2 and BSEP in GS group and PIS group were significantly lower than those in CT group (P < 0.05). Leptin stimulates HepG2 cells and increases the expressions of OB-Rb, AMPKa2, p-AMPKa2 and BSEP. Compund C inhibits the effect of leptin on OB-Rb, AMPKa2, p-AMPKa2 and BSEP in HepG2 cells. Conclusions Leptin is involved in the regulation of bile acid metabolism, and its abnormal effect in liver may be one of the mechanisms of cholelithiasis.

Key words: Leptin, Bile acid, BSEP, Cholelithiasis