title: Chenodeoxycholic acid stimulates glucagon-like peptide-1 secretion in patients after Roux-en-Y gastric bypass.
abstract: Postprandial secretion of glucagon-like peptide-1 (GLP-1) is enhanced after Roux-en-Y gastric bypass (RYGB), but the precise molecular mechanisms explaining this remain poorly understood. Plasma concentrations of bile acids (BAs) increase after RYGB, and BAs may act as molecular enhancers of GLP-1 secretion through activation of TGR5-receptors. We aimed to evaluate GLP-1 secretion after oral administration of the primary bile acid chenodeoxycholic acid (CDCA) and the secondary bile acid ursodeoxycholic acid (UDCA) (which are available for oral use) in RYGB-operated participants. Eleven participants (BMI 29.1 ± 1.2, age 37.0 ± 3.2 years, time from RYGB 32.3 ± 1.1 months, weight loss after RYGB 37.0 ± 3.1 kg) were studied in a placebo-controlled, crossover-study. On three different days, participants ingested (1) placebo (water), (2) UDCA 750 mg, (3) CDCA 1250 mg (highest recommended doses). Oral intake of CDCA increased plasma concentrations of GLP-1, C-peptide, glucagon, peptide YY, neurotensin, total bile acids, and fibroblast growth factor 19 significantly compared with placebo (allP< 0.05 for peak and positive incremental area-under-the-curve (piAUC)). All plasma hormone concentrations were unaffected by UDCA Neither UDCA nor CDCA changed glucose, cholecystokinin or glucose-dependent insulinotropic polypeptide (GIP) concentrations. In conclusion, our findings demonstrate that the primary bile acid chenodeoxycholic acid is able to enhance secretion of gut hormones when administered orally in RYGB-operated patients-even in the absence of nutrients.
authors.affiliation: Department of Endocrinology, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark.|NNF Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Signe
authors.initials: S
authors.lastname: Nielsen
authors.affiliation: Department of Endocrinology, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark.|NNF Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Maria S
authors.initials: MS
authors.lastname: Svane
authors.affiliation: NNF Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.|Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Rune E
authors.initials: RE
authors.lastname: Kuhre
authors.affiliation: Obesity Biology, Novo Nordisk A/S, Maaloev, Denmark.
authors.forename: Trine R
authors.initials: TR
authors.lastname: Clausen
authors.affiliation: Department of Surgical Gastroenterology, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark.
authors.forename: Viggo B
authors.initials: VB
authors.lastname: Kristiansen
authors.affiliation: Department of Clinical Biochemistry, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
authors.forename: Jens F
authors.initials: JF
authors.lastname: Rehfeld
authors.affiliation: NNF Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.|Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jens J
authors.initials: JJ
authors.lastname: Holst
authors.affiliation: Department of Endocrinology, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark.|NNF Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Sten
authors.initials: S
authors.lastname: Madsbad
authors.affiliation: Department of Endocrinology, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark kirstine.bojsen-moeller@regionh.dk.|NNF Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Kirstine N
authors.identifier: http://orcid.org/0000-0003-1962-5302
authors.initials: KN
authors.lastname: Bojsen-Moller
mesh_terms: D000284:Administration, Oral; D000328:Adult; D001647:Bile Acids and Salts / Q000097:blood; D001786:Blood Glucose; D002096:C-Peptide / Q000097:blood; D002635:Chenodeoxycholic Acid / Q000008:administration & dosage*; D018592:Cross-Over Studies; D005260:Female; D005346:Fibroblast Growth Factors / Q000097:blood; D015390:Gastric Bypass; D005934:Glucagon / Q000097:blood; D052216:Glucagon-Like Peptide 1 / Q000097:blood / Q000378:metabolism*; D006801:Humans; D008297:Male; D014580:Ursodeoxycholic Acid / Q000008:administration & dosage
chemical_list: D001647:Bile Acids and Salts; D001786:Blood Glucose; D002096:C-Peptide; C117476:FGF19 protein, human; D002635:Chenodeoxycholic Acid; D005346:Fibroblast Growth Factors; D014580:Ursodeoxycholic Acid; D052216:Glucagon-Like Peptide 1; D005934:Glucagon
keywords: 
  PYY
  ; Bile acids; GLP‐1; Roux‐en‐Y gastric bypass