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Cholecystectomy and risk of metabolic syndrome

Published:April 26, 2018DOI:https://doi.org/10.1016/j.ejim.2018.04.019

      Highlights

      • Cholecystectomy might cause metabolic consequences, including metabolic syndrome.
      • Pathways involving bile acids and their nuclear receptors play a critical role.
      • SNPs and epigenetic mechanisms could influence the development of metabolic syndrome.
      • Cholecystectomy should be considered after careful selection of patients.

      Abstract

      The gallbladder physiologically concentrates and stores bile during fasting and provides rhythmic bile secretion both during fasting and in the postprandial phase to solubilize dietary lipids and fat-soluble vitamins. Bile acids (BAs), major lipid components of bile, play a key role as signaling molecules in modulating gene expression related to cholesterol, BA, glucose and energy metabolism. Cholecystectomy is the most commonly performed surgical procedure worldwide in patients who develop symptoms and/or complications of cholelithiasis of any type. Cholecystectomy per se, however, might cause abnormal metabolic consequences, i.e., alterations in glucose, insulin (and insulin-resistance), lipid and lipoprotein levels, liver steatosis and the metabolic syndrome. Mechanisms are likely mediated by the abnormal transintestinal flow of BAs, producing metabolic signaling that acts without gallbladder rhythmic function and involves the BAs/farnesoid X receptor (FXR) and the BA/G protein-coupled BA receptor 1 (GPBAR-1) axes in the liver, intestine, brown adipose tissue and muscle. Alterations of intestinal microbiota leading to distorted homeostatic processes are also possible. According to this view, cholecystectomy, via BA-induced changes in the enterohepatic circulation, is a risk factor for the metabolic abnormalities and becomes another “fellow traveler” with, or another risk factor for the metabolic syndrome.

      Keywords

      Abbreviations:

      ASBT (apical sodium-dependent bile acid transporter), BAs (bile acids), CA (cholic acid), CDCA (chenodeoxycholic acid), DCA (deoxycholic acid), FGF (fibroblast growth factor), FXR (farnesoid X receptor), GPBAR-1 (G-protein-coupled bile acid receptor-1 (also known as TGR5)), IBABP (ileal bile acid-binding protein), JNK (c-Jun N-terminal kinase), LCA (lithocholic acid), NAFLD (non-alcoholic fatty liver disease), UDCA (ursodeoxycholic acid)
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