Activation of Human Brown Adipose Tissue by a beta 3-Adrenergic Receptor Agonist

作者：Cypess, Aaron M.^*; Weiner, Lauren S.; Roberts-Toler, Carla; Elia, Elisa Franquet; Kessler, Skyler H.; Kahn, Peter A.; English, Jeffrey; Chatman, Kelly; Trauger, Sunia A.; Doria, Alessandro; Kolodny, Gerald M.

来源：Cell Metabolism, 2015, 21(1): 33-38.

DOI：10.1016/j.cmet.2014.12.009

• SELECTIVE BETA(3)-ADRENOCEPTOR AGONIST
• ADULT HUMANS
• ADRENOCEPTOR AGONIST
• ENERGY-EXPENDITURE
• COLD-EXPOSURE
• DOUBLE-BLIND
• FAT
• THERMOGENESIS
• METABOLISM
• MIRABEGRON

Increasing energy expenditure through activation of endogenous brown adipose tissue (BAT) is a potential approach to treat obesity and diabetes. The class of beta 3-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 beta 3-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 F-18-fluorodeoxyglucose (F-18-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 beta 3-AR agonist can stimulate human BAT thermogenesis and may be a promising treatment for metabolic disease.

• 出版日期2015-1-6