Metabolic effects of cholecystectomy: Gallbladder ablation increases basal metabolic rate through G-protein Coupled Bile acid Receptor Gpbar1-dependent mechanisms in mice

Abstract

Background & Aims: Bile acids (BAs) regulate energy expenditure by activating G-protein Coupled Bile Acid Receptor Gpbar1/TGR5 by cAMP-dependent mechanisms. Cholecystectomy (XGB) increases BAs recirculation rates resulting in increased tissue exposure to BAs during the light phase of the diurnal cycle in mice. We aimed to determine: 1) the effects of XGB on basal metabolic rate (BMR) and 2) the roles of TGR5 on XGB-dependent changes in BMR. Methods: BMR was determined by indirect calorimetry in wild type and Tgr5 deficient (Tgr5 -/-) male mice. Bile flow and BAs secretion rates were measured by surgical diversion of biliary duct. Biliary BAs and cholesterol were quantified by enzymatic methods. BAs serum concentration and specific composition was determined by liquid chromatography/tandem mass spectrometry. Gene expression was determined by qPCR analysis. Results: XGB increased biliary BAs and cholesterol secretion rates, and elevated serum BAs concentration in wild type and Tgr5 -/- mice during the light phase of the diurnal cycle. BMR was ∼25% higher in cholecystectomized wild type mice (p <0.02), whereas no changes were detected in cholecystectomized Tgr5 -/- mice compared to wild-type animals. Conclusion: XGB increases BMR by TGR5-dependent mechanisms in mice.