Cholecystectomy and risk of metabolic syndrome

Eur J Intern Med. 2018 Jul:53:3-11. doi: 10.1016/j.ejim.2018.04.019. Epub 2018 Apr 26.


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: Bile acids; Cholecystectomy; Cholesterol; Enterohepatic circulation; Gallbladder; Gallstone disease; Nuclear receptors.

Publication types

  • Review

MeSH terms

  • Bile Acids and Salts / metabolism
  • Cholecystectomy*
  • Cholelithiasis / complications
  • Cholesterol / metabolism
  • Gallbladder / surgery
  • Gallstones / surgery*
  • Humans
  • Liver / metabolism
  • Liver / physiopathology
  • Metabolic Syndrome / etiology*
  • Metabolic Syndrome / metabolism*
  • Risk Factors


  • Bile Acids and Salts
  • Cholesterol