Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• Cell metabolism, 2015-01, Vol.21 (1), p.33-38

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2015

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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 18F-fluorodeoxyglucose (18F-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. [Display omitted] •The β3-AR agonist mirabegron acutely activates human BAT glucose uptake•The β3-AR agonist mirabegron acutely activates human WAT lipolysis•Mirabegron stimulates brown/beige fat in multiple depots.•Mirabegron-induced BAT activity is a predictor of whole-body thermogenesis Preclinical models indicate that activation of brown adipose tissue (BAT) can improve obesity and diabetes. Cypess et al. show that the β3-adrenergic receptor agonist mirabegron, currently approved for overactive bladder, stimulates human BAT thermogenesis and energy expenditure, suggesting that this pharmacological approach may be a promising treatment for metabolic disease.