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

Michael Scally MD

Doctor of Medicine
10+ Year Member
Highlights
· 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

Cypess AM, Weiner LS, Roberts-Toler V, Elía EF, Kessler SH, et al. Activation of Human Brown Adipose Tissue by a β3-Adrenergic Receptor Agonist. Cell Metabolism. http://www.cell.com/cell-metabolism/fulltext/S1550-4131(14)00560-9

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.
 
Back
Top