title: The Bile Acid Chenodeoxycholic Acid Increases Human Brown Adipose Tissue Activity.
abstract: The interest in brown adipose tissue (BAT) as a target to combat metabolic disease has recently been renewed with the discovery of functional BAT in humans. In rodents, BAT can be activated by bile acids, which activate type 2 iodothyronine deiodinase (D2) in BAT via the G-coupled protein receptor TGR5, resulting in increased oxygen consumption and energy expenditure. Here we examined the effects of oral supplementation of the bile acid chenodeoxycholic acid (CDCA) on human BAT activity. Treatment of 12 healthy female subjects with CDCA for 2 days resulted in increased BAT activity. Whole-body energy expenditure was also increased upon CDCA treatment. In vitro treatment of primary human brown adipocytes derived with CDCA or specific TGR5 agonists increased mitochondrial uncoupling and D2 expression, an effect that was absent in human primary white adipocytes. These findings identify bile acids as a target to activate BAT in humans.
authors.affiliation: Department of Human Biology and Human Movement Sciences, NUTRIM, School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht 6200 MD, the Netherlands; Department of General Surgery, NUTRIM, School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht 6200 MD, the Netherlands.
authors.forename: Evie P M
authors.initials: EP
authors.lastname: Broeders
authors.affiliation: Department of Human Biology and Human Movement Sciences, NUTRIM, School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht 6200 MD, the Netherlands.
authors.forename: Emmani B M
authors.initials: EB
authors.lastname: Nascimento
authors.affiliation: Department of Endocrinology, NUTRIM, School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht 6200 MD, the Netherlands.
authors.forename: Bas
authors.initials: B
authors.lastname: Havekes
authors.affiliation: Department of Nuclear Medicine, NUTRIM, School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht 6200 MD, the Netherlands.
authors.forename: Boudewijn
authors.initials: B
authors.lastname: Brans
authors.affiliation: Department of Human Biology and Human Movement Sciences, NUTRIM, School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht 6200 MD, the Netherlands.
authors.forename: Kay H M
authors.initials: KH
authors.lastname: Roumans
authors.affiliation: University of Lille, Institut Pasteur de Lille, Inserm UMR 1011, EGID, 59000 Lille, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Tailleux
authors.affiliation: Department of Human Biology and Human Movement Sciences, NUTRIM, School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht 6200 MD, the Netherlands.
authors.forename: Gert
authors.initials: G
authors.lastname: Schaart
authors.affiliation: University of Lille, Centre Universitaire de Mesures et d'Analyses, 59000 Lille, France.
authors.forename: Mostafa
authors.initials: M
authors.lastname: Kouach
authors.affiliation: University of Lille, Institut Pasteur de Lille, Inserm UMR1177, Biostructures and Drug Discovery, 59000 Lille, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Charton
authors.affiliation: University of Lille, Institut Pasteur de Lille, Inserm UMR1177, Biostructures and Drug Discovery, 59000 Lille, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: Deprez
authors.affiliation: Department of General Surgery, NUTRIM, School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht 6200 MD, the Netherlands.
authors.forename: Nicole D
authors.initials: ND
authors.lastname: Bouvy
authors.affiliation: Department of Nuclear Medicine, NUTRIM, School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht 6200 MD, the Netherlands; Nuclear Medicine, University Hospital Aachen, 52072 Aachen, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Mottaghy
authors.affiliation: University of Lille, Institut Pasteur de Lille, Inserm UMR 1011, EGID, 59000 Lille, France.
authors.forename: Bart
authors.initials: B
authors.lastname: Staels
authors.affiliation: Department of Human Biology and Human Movement Sciences, NUTRIM, School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht 6200 MD, the Netherlands.
authors.forename: Wouter D
authors.initials: WD
authors.lastname: van Marken Lichtenbelt
authors.affiliation: Department of Human Biology and Human Movement Sciences, NUTRIM, School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht 6200 MD, the Netherlands. Electronic address: p.schrauwen@maastrichtuniversity.nl.
authors.forename: Patrick
authors.initials: P
authors.lastname: Schrauwen
mesh_terms: D052437:Adipocytes, Brown / Q000187:drug effects / Q000378:metabolism; D002001:Adipose Tissue, Brown / Q000187:drug effects* / Q000378:metabolism*; D000284:Administration, Oral; D000328:Adult; D002478:Cells, Cultured; D002635:Chenodeoxycholic Acid / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D004734:Energy Metabolism / Q000187:drug effects*; D005260:Female; D006801:Humans; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D055815:Young Adult
chemical_list: C473772:GPBAR1 protein, human; D043562:Receptors, G-Protein-Coupled; D002635:Chenodeoxycholic Acid