title: Upregulation of hepatic bile acid synthesis via fibroblast growth factor 19 is defective in gallstone disease but functional in overweight individuals.
abstract: BACKGROUND
  Fibroblast growth factor 19 (FGF19) is an enteric hormone regulating bile acid de novo synthesis by sensing ileal bile acid flux. However, the role of FGF19 in cholelithiasis has not yet been elucidated and therefore is investigated in the present study.
  
  
  METHODS
  Total mRNA and protein were isolated from ileal biopsies and used for tissue expression analysis. FGF19, 7α-hydroxycholesterol (7α-OH-Chol), 27-hydroxycholesterol (27-OH-Chol), and different bile acids were determined in the blood samples.
  
  
  RESULTS
  FGF19 serum levels did not differ between gallstone carriers and controls but were significantly decreased in the overweight individuals (-32%, p = 0.0002), irrespective of gallstone status (normalweight to overweight controls -29%, p = 0.0017; normalweight to overweight gallstone carriers -44%, p = 0.0338), and correlated inversely with bodyweight (p < 0.0001, ρ = -0.3317). Compared to non-overweight controls, apical sodium-dependent bile acid transporter expression was significantly diminished in the non-overweight gallstone carriers (-42%, P mRNA = 0.0393; -52%, p protein = 0.0169) as well as in the overweight controls (-24%, P mRNA = 0.0148; -43%, p protein = 0.0017). FGF19 expression varied widely and was similar in all groups. A significant negative correlation was noted between 7α-OH-Chol, 27-OH-Chol, and FGF19 serum levels (p < 0.01; ρ7α-OH-Chol = -0.2155; ρ27-OH-Chol = -0.2144) in obesity.
  
  
  CONCLUSIONS
  Upregulation of hepatic bile acid synthesis via FGF 19 is defective in gallstone disease but functional in overweight individuals.
authors.affiliation: Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology and University of Tuebingen, Stuttgart, Germany.
authors.forename: Olga
authors.initials: O
authors.lastname: Renner
authors.affiliation: Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology and University of Tuebingen, Stuttgart, Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Harsch
authors.affiliation: University Hospital Regensburg, Regensburg, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Matysik
authors.affiliation: Institute for Clinical Chemistry and Clinical Pharmacology, Laboratory for Special Lipid Diagnostics, University Hospital Bonn, Bonn, Germany.
authors.forename: Dieter
authors.initials: D
authors.lastname: Lütjohann
authors.affiliation: University Hospital Regensburg, Regensburg, Germany.
authors.forename: Gerd
authors.initials: G
authors.lastname: Schmitz
authors.affiliation: Department of Gastroenterology, Robert Bosch Hospital, Stuttgart, Germany.
authors.forename: Eduard F
authors.initials: EF
authors.lastname: Stange
keywords: Bile acid transport/absorption; bodyweight; entric hormone; expression; intestine