The role of bile acids signaling as regulator of cholesterol metabolism in normal and diseased gallbladder

Abstract

Background: Bile acids (BAs) are cholesterol-derived steroid acids and constitute one of the major components of bile. They are known to have a part in assimilation of lipid, cholesterol and fat dissolvable vitamins. Recent researches have revealed that bile acids operate as signaling molecules that regulate the metabolism of bile acids, fatty acids, glucose homeostasis, lipoproteins and energy metabolism via interfering with nuclear and surface receptors.Objective: to investigate the role of bile acids signaling in farnesoid x receptor (FXR) / fibroblast growth factor(FGF)19 pathway in cholesterol metabolism in normal and gallstone gallbladders.Methodology: Thirty individuals participated in this study and were separated into 2 groups, each group 15 individuals. Group (i) normal group: adult persons with healthy gallbladder underwent elective cholecystectomy as a part of another procedure as they were living-donor liver transplant, and group(ii) gallstone group (GS): adult persons underwent elective cholecystectomy for gallstone disease. Serum concentration of cholesterol, Fibroblast growth factor 19 (FGF19), Cholesterol 7α-hydroxylase enzyme (CYP7A1) and Sterol 12-hydroxylase (CYP8B1) and bile concentration of Phospholipid, Cholic acid (CA), Deoxycholic acid (DCA) and Chenodeoxycholic acid (CDCA) were determined.Results: Concentration of cholesterol,CYP7A1 and CYP8B1 in the serum as well as concentration of cholesterol in bile were all significantly higher in gallstone group. While, concentration of FGF19 in serum as well as concentration of phospholipids, CA, DCA and CDCA in bile were all significantly lower in gallstone group. Conclusion:The bile acids/FXR/FGF19 pathway regulates cholesterol metabolism and prevents gallstone development by reducing the levels.