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Cited by 138

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Regulation of Human Adipose Tissue Activation, Gallbladder Size, and Bile Acid Metabolism by a β3-Adrenergic Receptor Agonist

Baskin, Alison S., Linderman, Joyce D., Brychta, Robert J., McGehee, Suzanne, Anflick-Chames, Esti, Cero, Cheryl, Johnson, James W., O’Mara, Alana E., Fletcher, Laura A., Leitner, Brooks P., Duckworth, Courtney J., Huang, Shan, Cai, Hongyi, Garraffo, H. Martin, Millo, Corina M., Dieckmann, William, Tolstikov, Vladimir, Chen, Emily Y., Gao, Fei, Narain, Niven R., Kiebish, Michael A., Walter, Peter J., Herscovitch, Peter, Chen, Kong Y., Cypess, Aaron M.·2018·Diabetes
DOI 10.2337/db18-0462
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Abstract

β3-adrenergic receptor (AR) agonists are approved to treat only overactive bladder. However, rodent studies suggest that these drugs could have other beneficial effects on human metabolism. We performed tissue receptor profiling and showed that the human β3-AR mRNA is also highly expressed in gallbladder and brown adipose tissue (BAT). We next studied the clinical implications of this distribution in 12 healthy men given one-time randomized doses of placebo, the approved dose of 50 mg, and 200 mg of the β3-AR agonist mirabegron. There was a more-than-dose-proportional increase in BAT metabolic activity as measured by [18F]-2-fluoro-D-2-deoxy-d-glucose positron emission tomography/computed tomography (medians 0.0 vs. 18.2 vs. 305.6 mL ⋅ mean standardized uptake value [SUVmean] ⋅ g/mL). Only the 200-mg dose elevated both nonesterified fatty acids (68%) and resting energy expenditure (5.8%). Previously undescribed increases in gallbladder size (35%) and reductions in conjugated bile acids were also discovered. Therefore, besides urinary bladder relaxation, the human β3-AR contributes to white adipose tissue lipolysis, BAT thermogenesis, gallbladder relaxation, and bile acid metabolism. This physiology should be considered in the development of more selective β3-AR agonists to treat obesity-related complications.

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Research works printed but not linked: 45

  1. Liu, 1998, Mechanisms of the antidiabetic effects of the beta 3-adrenergic agonist CL-316243 in obese Zucker-ZDF rats, Am J Physiol, 274, R1212
  2. Cypess, 2012, Cold but not sympathomimetics activates human brown adipose tissue in vivo, Proc Natl Acad Sci U S A, 109, 10001, 10.1073/pnas.1207911109 · DOI · Paper page
  3. Svensson, 2016, A secreted Slit2 fragment regulates adipose tissue thermogenesis and metabolic function, Cell Metab, 23, 454, 10.1016/j.cmet.2016.01.008 · DOI
  4. Wang, 2014, The brown fat-enriched secreted factor Nrg4 preserves metabolic homeostasis through attenuation of hepatic lipogenesis, Nat Med, 20, 1436, 10.1038/nm.3713 · DOI
  5. Villarroya, 2017, Brown adipose tissue as a secretory organ, Nat Rev Endocrinol, 13, 26, 10.1038/nrendo.2016.136 · DOI
  6. Lynes, 2017, The cold-induced lipokine 12,13-diHOME promotes fatty acid transport into brown adipose tissue, Nat Med, 23, 631, 10.1038/nm.4297 · DOI · Paper page
  7. Arch, 2011, Challenges in β(3)-adrenoceptor agonist drug development, Ther Adv Endocrinol Metab, 2, 59, 10.1177/2042018811398517 · DOI
  8. Cawthorne, 1992, BRL 35135, a potent and selective atypical beta-adrenoceptor agonist, Am J Clin Nutr, 55, 252S, 10.1093/ajcn/55.1.252s · DOI
  9. Cypess, 2015, Activation of human brown adipose tissue by a β3-adrenergic receptor agonist, Cell Metab, 21, 33, 10.1016/j.cmet.2014.12.009 · DOI · Paper page
  10. Malik, 2012, Proarrhythmic safety of repeat doses of mirabegron in healthy subjects: a randomized, double-blind, placebo-, and active-controlled thorough QT study, Clin Pharmacol Ther, 92, 696, 10.1038/clpt.2012.181 · DOI
  11. Cypess, 2009, Identification and importance of brown adipose tissue in adult humans, N Engl J Med, 360, 1509, 10.1056/NEJMoa0810780 · DOI · Paper page
  12. Chen, 2013, Brown fat activation mediates cold-induced thermogenesis in adult humans in response to a mild decrease in ambient temperature, J Clin Endocrinol Metab, 98, E1218, 10.1210/jc.2012-4213 · DOI
  13. Tolstikov, 2014, Metabolomics analysis of metabolic effects of nicotinamide phosphoribosyltransferase (NAMPT) inhibition on human cancer cells, PLoS One, 9, e114019, 10.1371/journal.pone.0114019 · DOI
  14. Drolet, 2017, Metabolites, 7, 35, 10.3390/metabo7030035 · DOI
  15. Xia, 2016, Using metaboAnalyst 3.0 for comprehensive metabolomics data analysis, 14.10.11
  16. Chapple, 2013, A phase II dose-ranging study of mirabegron in patients with overactive bladder, Int Urogynecol J, 24, 1447, 10.1007/s00192-013-2042-x · DOI
  17. Propping, 2015, β-Adrenoceptor-mediated relaxation of carbachol-pre-contracted mouse detrusor, Urol Int, 95, 92, 10.1159/000369075 · DOI
  18. Lidell, 2013, Evidence for two types of brown adipose tissue in humans, Nat Med, 19, 631, 10.1038/nm.3017 · DOI · Paper page
  19. Dmitrieva, 2013, A day-centered approach to modeling cortisol: diurnal cortisol profiles and their associations among U.S. adults, Psychoneuroendocrinology, 38, 2354, 10.1016/j.psyneuen.2013.05.003 · DOI
  20. Liu, 2015, Modeling diurnal hormone profiles by hierarchical state space models, Stat Med, 34, 3223, 10.1002/sim.6579 · DOI
  21. Park, 2015, Physiology of leptin: energy homeostasis, neuroendocrine function and metabolism, Metabolism, 64, 24, 10.1016/j.metabol.2014.08.004 · DOI
  22. Barrera, 2011, GLP-1 and energy balance: an integrated model of short-term and long-term control, Nat Rev Endocrinol, 7, 507, 10.1038/nrendo.2011.77 · DOI · Paper page
  23. Yu, 2011, Circadian rhythm of circulating fibroblast growth factor 21 is related to diurnal changes in fatty acids in humans, Clin Chem, 57, 691, 10.1373/clinchem.2010.155184 · DOI
  24. Brabant, 1986, Pulsatile pattern of thyrotropin-release in normal men, Clin Chim Acta, 155, 159, 10.1016/0009-8981(86)90277-9 · DOI
  25. Gavrilova, 2000, Lack of responses to a beta3-adrenergic agonist in lipoatrophic A-ZIP/F-1 mice, Diabetes, 49, 1910, 10.2337/diabetes.49.11.1910 · DOI
  26. Kitamura, 1972, Hemodynamic correlates of myocardial oxygen consumption during upright exercise, J Appl Physiol, 32, 516, 10.1152/jappl.1972.32.4.516 · DOI · Paper page
  27. Redman, 2007, Lack of an effect of a novel beta3-adrenoceptor agonist, TAK-677, on energy metabolism in obese individuals: a double-blind, placebo-controlled randomized study, J Clin Endocrinol Metab, 92, 527, 10.1210/jc.2006-1740 · DOI · Paper page
  28. Sacco, 2012, Mirabegron: a review of recent data and its prospects in the management of overactive bladder, Ther Adv Urol, 4, 315, 10.1177/1756287212457114 · DOI
  29. Chapple, 2014, Mirabegron 50 mg once-daily for the treatment of symptoms of overactive bladder: an overview of efficacy and tolerability over 12 weeks and 1 year, 960
  30. Whittle, 2012, BMP8B increases brown adipose tissue thermogenesis through both central and peripheral actions, Cell, 149, 871, 10.1016/j.cell.2012.02.066 · DOI · Paper page
  31. Cypess, 2013, Anatomical localization, gene expression profiling and functional characterization of adult human neck brown fat, Nat Med, 19, 635, 10.1038/nm.3112 · DOI · Paper page
  32. Porter, 2016, Human and mouse brown adipose tissue mitochondria have comparable UCP1 function, Cell Metab, 24, 246, 10.1016/j.cmet.2016.07.004 · DOI · Paper page
  33. Oriowo, 1999, Functional characterization of beta-adrenoceptors mediating relaxation in sheep gallbladder, Fundam Clin Pharmacol, 13, 187, 10.1111/j.1472-8206.1999.tb00337.x · DOI
  34. Trebicka, 2009, Role of beta3-adrenoceptors for intrahepatic resistance and portal hypertension in liver cirrhosis, Hepatology, 50, 1924, 10.1002/hep.23222 · DOI
  35. Samuel, 1968, Absorption of bile acids from the large bowel in man, J Clin Invest, 47, 2070, 10.1172/JCI105892 · DOI
  36. Dawson, 2009, Bile acid transporters, J Lipid Res, 50, 2340, 10.1194/jlr.R900012-JLR200 · DOI
  37. Repa, 2000, Regulation of absorption and ABC1-mediated efflux of cholesterol by RXR heterodimers, Science, 289, 1524, 10.1126/science.289.5484.1524 · DOI · Paper page
  38. Goodwin, 2000, A regulatory cascade of the nuclear receptors FXR, SHP-1, and LRH-1 represses bile acid biosynthesis, Mol Cell, 6, 517, 10.1016/S1097-2765(00)00051-4 · DOI · Paper page
  39. Chen, 1997, Gallbladder relaxation in patients with pigment and cholesterol stones, Gastroenterology, 113, 930, 10.1016/S0016-5085(97)70189-6 · DOI
  40. Broeders, 2015, The bile acid chenodeoxycholic acid increases human Brown adipose tissue activity, Cell Metab, 22, 418, 10.1016/j.cmet.2015.07.002 · DOI
  41. Deng, 2017, An adipo-biliary-uridine axis that regulates energy homeostasis, Science, 355, eaaf5375, 10.1126/science.aaf5375 · DOI
  42. Jiang, 2015, Intestinal farnesoid X receptor signaling promotes nonalcoholic fatty liver disease, J Clin Invest, 125, 386, 10.1172/JCI76738 · DOI · Paper page
  43. Berbée, 2015, Brown fat activation reduces hypercholesterolaemia and protects from atherosclerosis development, Nat Commun, 6, 6356, 10.1038/ncomms7356 · DOI
  44. Wang, 2014, The brown fat-enriched secreted factor Nrg4 preserves metabolic homeostasis through attenuation of hepatic lipogenesis, Nat Med, 20, 1436, 10.1038/nm.3713 · DOI
  45. Porez, 2012, Bile acid receptors as targets for the treatment of dyslipidemia and cardiovascular disease, J Lipid Res, 53, 1723, 10.1194/jlr.R024794 · DOI · Paper page

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Metadata

Authors
Baskin, A. S., Linderman, J. D., Brychta, R. J., McGehee, S., Anflick-Chames, E., Cero, C., Johnson, J. W., O’Mara, A. E., Fletcher, L. A., Leitner, B. P., Duckworth, C. J., Huang, S., Cai, H., Garraffo, H. M., Millo, C. M., Dieckmann, W., Tolstikov, V., Chen, E. Y., Gao, F., Narain, N. R., Kiebish, M. A., Walter, P. J., Herscovitch, P., Chen, K. Y., & Cypess, A. M.
Venue
Diabetes
Publisher
American Diabetes Association
Published
2018-07-06
Volume
67
Issue
10
Pages
2113-2125
ISSN
  • 0012-1797
  • 1939-327X
DOI
10.2337/db18-0462
Cited by
138
References
13
Language
en
Licence
www.diabetesjournals.org/content/license (vor, 76 d)
Funders
NIDDK (DK-075112, DK-075116, DK-071013, DK-071014)

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