title: Activation of human brown adipose tissue by a β3-adrenergic receptor agonist.
abstract: Increasing energy expenditure through activation of endogenous brown adipose tissue (BAT) is a potential approach to treat obesity and diabetes. The class of β3-adrenergic receptor (AR) agonists stimulates rodent BAT, but this activity has never been demonstrated in humans. Here we determined the ability of 200 mg oral mirabegron (Myrbetriq, Astellas Pharma, Inc.), a β3-AR agonist currently approved to treat overactive bladder, to stimulate BAT as compared to placebo. Mirabegron led to higher BAT metabolic activity as measured via (18)F-fluorodeoxyglucose ((18)F-FDG) using positron emission tomography (PET) combined with computed tomography (CT) in all twelve healthy male subjects (p = 0.001), and it increased resting metabolic rate (RMR) by 203 ± 40 kcal/day (+13%; p = 0.001). BAT metabolic activity was also a significant predictor of the changes in RMR (p = 0.006). Therefore, a β3-AR agonist can stimulate human BAT thermogenesis and may be a promising treatment for metabolic disease.
authors.affiliation: Section of Integrative Physiology and Metabolism, Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA. Electronic address: Aaron.Cypess@joslin.harvard.edu.
authors.forename: Aaron M
authors.initials: AM
authors.lastname: Cypess
authors.affiliation: Section of Integrative Physiology and Metabolism, Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Lauren S
authors.initials: LS
authors.lastname: Weiner
authors.affiliation: Section of Integrative Physiology and Metabolism, Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Carla
authors.initials: C
authors.lastname: Roberts-Toler
authors.affiliation: Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Elisa
authors.initials: E
authors.lastname: Franquet Elía
authors.affiliation: Section of Integrative Physiology and Metabolism, Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Skyler H
authors.initials: SH
authors.lastname: Kessler
authors.affiliation: Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Kahn
authors.affiliation: Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: English
authors.affiliation: Small Molecule Mass Spectrometry Facility, FAS Division of Science, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Kelly
authors.initials: K
authors.lastname: Chatman
authors.affiliation: Small Molecule Mass Spectrometry Facility, FAS Division of Science, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Sunia A
authors.initials: SA
authors.lastname: Trauger
authors.affiliation: Section of Genetics and Epidemiology, Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Doria
authors.affiliation: Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Gerald M
authors.initials: GM
authors.lastname: Kolodny
mesh_terms: D000083:Acetanilides / Q000032:analysis / Q000494:pharmacology / Q000627:therapeutic use*; D002001:Adipose Tissue, Brown / Q000187:drug effects / Q000378:metabolism*; D000322:Adrenergic Agonists / Q000032:analysis / Q000494:pharmacology / Q000627:therapeutic use*; D001481:Basal Metabolism / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D019788:Fluorodeoxyglucose F18 / Q000737:chemistry / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006801:Humans; D008297:Male; D009765:Obesity / Q000188:drug therapy*; D049268:Positron-Emission Tomography; D022702:Receptors, Adrenergic, beta-3 / Q000737:chemistry / Q000378:metabolism*; D053719:Tandem Mass Spectrometry; D013844:Thiazoles / Q000032:analysis / Q000494:pharmacology / Q000627:therapeutic use*; D014057:Tomography, X-Ray Computed; D055815:Young Adult
chemical_list: D000083:Acetanilides; D000322:Adrenergic Agonists; D022702:Receptors, Adrenergic, beta-3; D013844:Thiazoles; D019788:Fluorodeoxyglucose F18; D005947:Glucose; C520025:mirabegron