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Clinical Trial
. 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

Free PMC article
Clinical Trial

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

Aaron M Cypess et al. Cell Metab. .
Free PMC article


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.


Figure 1
Figure 1. Metabolic Effects of the β3-AR Agonist Mirabegron
(A) PET images of a 21-year-old man who was given placebo (left) or 200 mg of the β3-AR agonist mirabegron (right). Twelve male subjects were given placebo or 200 mg mirabegron. (B) BAT metabolic activity as reflected by 18F-FDG uptake. (C) Resting metabolic rate. (D) Heart rate. (E) Systolic BP. (F) Diastolic BP. Each circle represents a single subject, and the numbers correspond to subject identification number in Figure S2. The dashes represent the mean. See also Figure S2.
Figure 2
Figure 2. Tissue Glucose Uptake
18F-FDG uptake in the twelve volunteers when given placebo or 200 mg mirabegron is shown for different tissues. Each circle represents a single subject. (A) Myocardium. (B) Subcutaneous WAT. (C) Skeletal muscle. (D) Liver. See also Table S1.
Figure 3
Figure 3. Predictors of Resting Metabolic Rate
(A) Placebo-induced BAT activity. (B) Two-hundred milligram mirabegron-induced BAT activity. (C) Body fat mass with placebo. (D) Body fat mass with 200 mg mirabegron. See also Figure S3.

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