The role of bile salts in liver regeneration

A growing body of evidence has demonstrated that bile salts are important for liver regeneration following partial hepatectomy. The relative bile salt overload after partial liver resection causes activation of bile salt receptors in non-parenchymal (viz. the plasma membrane receptor TGR5) and parenchymal (viz. the intracellular receptor FXR) cells in the liver, thus, providing signals to the regenerative process. Impaired bile salt signaling in mice with genetic deficiency of Tgr5 or Fxr results in delayed liver regeneration after partial hepatectomy, and is accompanied by mortality in case of Fxr knock-out mice. Conversely, compensatory liver re-growth in hepatectomized mice can be stimulated by feeding of bile salts or alisol B 23-acetate, a natural triterpenoid agonist of Fxr. A large number of animal studies underscore the importance of strict maintenance of bile salt homeostasis for proper progression of liver regeneration. Both ileal and hepatic Fxr play a key role in regulation of bile salt homeostasis and, thus, preventing hepatotoxicity caused by excessive levels of bile salts. They further contribute to liver regeneration by induction of mitogenic factors. Agents that target bile salt receptors hold promise as drugs to stimulate liver regeneration in selected patients.