title: Stimulation of apical sodium-dependent bile acid transporter expands the bile acid pool and generates bile acids with positive feedback properties.
abstract: BACKGROUND
  Bile acid synthesis has been considered a prototype for how a physiological process is controlled by end product feedback inhibition. By this feedback inhibition, bile acid concentrations are kept within safe ranges. However, careful examination of published rodent data strongly suggests that bile acid synthesis is also under potent positive feedback control by hydrophilic bile acids.
  
  
  CONCLUSIONS
  Current concepts on the regulation of bile acid synthesis are derived from mouse models. Recent data have shown that mice have farnesoid X receptor (FXR) antagonistic bile acids capable of quenching responses elicited by FXR agonistic bile acids. This is important to recognize to understand the regulation of bile acid synthesis in the mouse, and in particular to clarify if mouse model findings are valid also in the human situation.
  
  
  CONCLUSIONS
  In addition to classic end product feedback inhibition, regulation of bile acid synthesis in the mouse largely appears also to be driven by changes in hepatic levels of murine bile acids such as α- and β-muricholic acids. This has not been previously recognized. Stimulated bile acid synthesis or induction of the apical sodium-dependent bile acid transporter in the intestine, increase the availability of chenodeoxycholic acid in the liver, thereby promoting hepatic conversion of this bile acid into muricholic acids. Recognition of these mechanisms is essential for understanding the regulation of bile acid synthesis in the mouse, and for our awareness of important species differences in the regulation of bile acid synthesis in mice and humans.
authors.affiliation: Metabolism Unit, Department of Endocrinology, Metabolism and Diabetes, KI/AZ Integrated CardioMetabolic Center, Department of Medicine, and Molecular Nutrition Unit, Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Mats
authors.initials: M
authors.lastname: Rudling
authors.forename: Ylva
authors.initials: Y
authors.lastname: Bonde
mesh_terms: D000667:Ampicillin / Q000494:pharmacology; D000818:Animals; D001647:Bile Acids and Salts / Q000096:biosynthesis*; D002635:Chenodeoxycholic Acid / Q000096:biosynthesis / Q000494:pharmacology; D002790:Cholesterol 7-alpha-Hydroxylase / Q000235:genetics; D019826:Cholic Acid / Q000494:pharmacology; D002793:Cholic Acids / Q000378:metabolism; D003840:Deoxycholic Acid / Q000494:pharmacology; D004195:Disease Models, Animal; D025461:Feedback, Physiological / Q000187:drug effects; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D029363:Organic Anion Transporters, Sodium-Dependent / Q000378:metabolism*; D010641:Phenotype; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists / Q000037:antagonists & inhibitors; D027981:Symporters / Q000378:metabolism*; D000099150:Receptor, Farnesoid X-Activated
chemical_list: D000667:Ampicillin; D001647:Bile Acids and Salts; D002635:Chenodeoxycholic Acid; D002790:Cholesterol 7-alpha-Hydroxylase; D019826:Cholic Acid; D002793:Cholic Acids; D003840:Deoxycholic Acid; D029363:Organic Anion Transporters, Sodium-Dependent; D018160:Receptors, Cytoplasmic and Nuclear; D027981:Symporters; D000099150:Receptor, Farnesoid X-Activated; C071908:sodium-bile acid cotransporter; C004821:muricholic acid; C502772:Cyp7a1 protein, mouse