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

Activation of human brown adipose tissue by a β3-adrenergic receptor agonist.

Author information

1
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.
2
Section of Integrative Physiology and Metabolism, Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA.
3
Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
4
Albert Einstein College of Medicine, Bronx, NY 10461, USA.
5
Small Molecule Mass Spectrometry Facility, FAS Division of Science, Harvard University, Cambridge, MA 02138, USA.
6
Section of Genetics and Epidemiology, Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA.

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.

PMID:
25565203
PMCID:
PMC4298351
DOI:
10.1016/j.cmet.2014.12.009
[Indexed for MEDLINE]
Free PMC Article

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