Activation of Human Brown Adipose Tissue by a β3-adrenergic Receptor Agonist

Cell Metab. 2015 Jan 6;21(1):33-8. doi: 10.1016/j.cmet.2014.12.009.

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.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Acetanilides / analysis
  • Acetanilides / pharmacology
  • Acetanilides / therapeutic use*
  • Adipose Tissue, Brown / drug effects
  • Adipose Tissue, Brown / metabolism*
  • Adrenergic Agonists / analysis
  • Adrenergic Agonists / pharmacology
  • Adrenergic Agonists / therapeutic use*
  • Basal Metabolism / drug effects
  • Chromatography, High Pressure Liquid
  • Fluorodeoxyglucose F18 / chemistry
  • Fluorodeoxyglucose F18 / metabolism
  • Glucose / metabolism
  • Humans
  • Male
  • Obesity / drug therapy*
  • Positron-Emission Tomography
  • Receptors, Adrenergic, beta-3 / chemistry
  • Receptors, Adrenergic, beta-3 / metabolism*
  • Tandem Mass Spectrometry
  • Thiazoles / analysis
  • Thiazoles / pharmacology
  • Thiazoles / therapeutic use*
  • Tomography, X-Ray Computed
  • Young Adult

Substances

  • Acetanilides
  • Adrenergic Agonists
  • Receptors, Adrenergic, beta-3
  • Thiazoles
  • Fluorodeoxyglucose F18
  • Glucose
  • mirabegron