@article{429f502751ca47c285e19cee8b1684eb,
title = "Chronic mirabegron treatment increases human brown fat, HDL cholesterol, and insulin sensitivity",
abstract = "BACKGROUND. Mirabegron is a β3-adrenergic receptor (β3-AR) agonist approved only for the treatment of overactive bladder. Encouraging preclinical results suggest that β3-AR agonists could also improve obesity-related metabolic disease by increasing brown adipose tissue (BAT) thermogenesis, white adipose tissue (WAT) lipolysis, and insulin sensitivity. METHODS. We treated 14 healthy women of diverse ethnicities (27.5 ± 1.1 years of age, BMI of 25.4 ± 1.2 kg/m2) with 100 mg mirabegron (Myrbetriq extended-release tablet, Astellas Pharma) for 4 weeks in an open-label study. The primary endpoint was the change in BAT metabolic activity as measured by [18F]-2-fluoro-d-2-deoxy-d-glucose (18F-FDG) PET/CT. Secondary endpoints included resting energy expenditure (REE), plasma metabolites, and glucose and insulin metabolism as assessed by a frequently sampled intravenous glucose tolerance test. RESULTS. Chronic mirabegron therapy increased BAT metabolic activity. Whole-body REE was higher, without changes in body weight or composition. Additionally, there were elevations in plasma levels of the beneficial lipoprotein biomarkers HDL and ApoA1, as well as total bile acids. Adiponectin, a WAT-derived hormone that has antidiabetic and antiinflammatory capabilities, increased with acute treatment and was 35% higher upon completion of the study. Finally, an intravenous glucose tolerance test revealed higher insulin sensitivity, glucose effectiveness, and insulin secretion. CONCLUSION. These findings indicate that human BAT metabolic activity can be increased after chronic pharmacological stimulation with mirabegron and support the investigation of β3-AR agonists as a treatment for metabolic disease.",
author = "O'Mara, {Alana E.} and Johnson, {James W.} and Linderman, {Joyce D.} and Brychta, {Robert J.} and Suzanne McGehee and Fletcher, {Laura A.} and Fink, {Yael A.} and Devika Kapuria and Cassimatis, {Thomas M.} and Nathan Kelsey and Cheryl Cero and Sater, {Zahraa Abdul} and Francesca Piccinini and Baskin, {Alison S.} and Leitner, {Brooks P.} and Hongyi Cai and Millo, {Corina M.} and William Dieckmann and Mary Walter and Javitt, {Norman B.} and Yaron Rotman and Walter, {Peter J.} and Marilyn Ader and Bergman, {Richard N.} and Peter Herscovitch and Chen, {Kong Y.} and Cypess, {Aaron M.}",
note = "Funding Information: This work was supported by grants from the Intramural Research Program of the NIDDK, NIH (DK075112, DK075116, DK071013, and DK071014). This work was supported by the Intramural Research Program of the NIDDK, NIH (DK075112, DK075116, DK071013, and DK071014). We are grateful for the excellent support provided by the NIH Metabolic Clinical Research Unit nursing team; the NIH Clinical Center Nutrition Department; the NIDDK Clinical Laboratory Core Lab; the NIH Department of Laboratory Medicine; the research pharmacy; and the PET technologists. We thank Douglas Rosing for acting as the independent internal data safety monitor. We also wish to thank Wouter van Marken Lichtenbelt for sharing his team's data so that we could perform our sample-size calculations; Sushil Rane and his laboratory for the gift of human islets; Paul Wakim and Sungyoung Auh for their biostatistical advice; Marc Reitman, Jack Yanovski, and Clifton Bogardus for their discussions about the data and their implications; Anne Sumner, Sushil Rane, and Gordon Weir for their guidance in interpreting the FSIGT data; and David Sacks and Jeff Basilio for their advice on measuring tissue glycemia. We are especially grateful to our volunteers for their commitment to this study. Funding Information: FUNDING. This work was supported by grants from the Intramural Research Program of the NIDDK, NIH (DK075112, DK075116, DK071013, and DK071014). Funding Information: This work was supported by the Intramural Research Program of the NIDDK, NIH (DK075112, DK075116, DK071013, and DK071014). We are grateful for the excellent support provided by the NIH Metabolic Clinical Research Unit nursing team; the NIH Clinical Center Nutrition Department; the NIDDK Clinical Laboratory Core Lab; the NIH Department of Laboratory Medicine; the research pharmacy; and the PET technologists. We thank Douglas Rosing for acting as the independent internal data safety monitor. We also wish to thank Wouter van Marken Lichtenbelt for sharing his team{\textquoteright}s data so that we could perform our sample-size calculations; Sushil Rane and his laboratory for the gift of human islets; Paul Wakim and Sungyoung Auh for their biostatistical advice; Marc Reitman, Jack Yanovski, and Clifton Bogar-dus for their discussions about the data and their implications; Anne Sumner, Sushil Rane, and Gordon Weir for their guidance in interpreting the FSIGT data; and David Sacks and Jeff Basilio for their advice on measuring tissue glycemia. We are especially grateful to our volunteers for their commitment to this study. Publisher Copyright: {\textcopyright} 2020, American Society for Clinical Investigation.",
year = "2020",
month = may,
day = "1",
doi = "10.1172/JCI131126",
language = "English",
volume = "130",
pages = "2209--2219",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
number = "5",
}