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

By A. Cypess, Lauren S Weiner, C. Roberts-Toler, E. F. Elía, Skyler Kessler, Peter Kahn, Jeffrey English, K. Chatman, S. Trauger, A. Doria and 1 more. Cell Metabolism, 2015

943 citations recorded by the source corpus.

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 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.

Subfields: Cell Biology, Physiology, Rehabilitation

View Paper: https://www.semanticscholar.org/paper/6759ac500747c21f76b57503f5017918392dcad3

How researchers see this paper

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In Cell Biology

1. P. Seale
2. B. Spiegelman
3. S. Kajimura

In Physiology

1. P. Seale
2. S. Kajimura
3. B. Spiegelman
4. A. Chait
5. Laura J. den Hartigh
6. E. Rosen
7. L. Sidossis
8. R. Scarpulla

In Rehabilitation

1. S. Kajimura
2. B. Spiegelman
3. P. Seale

Citations in the corpus

• Adipose Tissue Distribution, Inflammation and Its Metabolic Consequences, Including Diabetes and Cardiovascular Disease (2020, background): “Efforts to enhance BAT activation in humans consist of intermittent regular cold exposure, introduction of β3-adrenergic receptor agonists, and exercise (29, 357).”
• Intermittent Fasting Promotes White Adipose Browning and Decreases Obesity by Shaping the Gut Microbiota (2017, neutral): “The mechanism by which EODF induces higher energy expenditure might differ from that of cold exposure; cold exposure is closely tied to b-AR signaling (Cypess et al., 2015; Mund and Frishman, 2013), while fasting is known to suppress norepinephrine turnover (Knehans and Romsos, 1983) and norepinephr”
• Brown and beige fat: Physiological roles beyond heat-generation (2015, background): “Recently, Cypess and colleagues reported that oral administration of a selective b3-AR agonist Mirabegron robustly stimulated glucose uptake in the BAT depots in healthy adult humans, in parallel with an increase in resting metabolic rate (Cypess et al., 2015).”