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

2015; Cell Press; Volume: 21; Issue: 1 Linguagem: Inglês

10.1016/j.cmet.2014.12.009

1932-7420

Aaron M. Cypess, Lauren S Weiner, Carla Roberts‐Toler, Elisa Franquet Elía, Skyler Kessler, Peter A. Kahn, Jeffrey English, Kelly Chatman, Sunia A. Trauger, Alessandro Doria, Gerald M. Kolodny,

Muscle metabolism and nutrition

Summary 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.