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

被引：113

作者：

Baskin, Alison S. ^{[1
]}

Linderman, Joyce D. ^{[1
]}

Brychta, Robert J. ^{[1
]}

McGehee, Suzanne ^{[1
]}

Anflick-Chames, Esti ^{[1
]}

Cero, Cheryl ^{[1
]}

Johnson, James W. ^{[1
]}

O'Mara, Alana E. ^{[1
]}

Fletcher, Laura A. ^{[1
]}

Leitner, Brooks P. ^{[1
]}

Duckworth, Courtney J. ^{[1
]}

Huang, Shan ^{[1
]}

Cai, Hongyi ^{[2
]}

Garraffo, H. Martin ^{[2
]}

Millo, Corina M. ^{[3
]}

Dieckmann, William ^{[3
]}

Tolstikov, Vladimir ^{[4
]}

Chen, Emily Y. ^{[4
]}

Gao, Fei ^{[4
]}

Narain, Niven R. ^{[4
]}

Kiebish, Michael A. ^{[4
]}

Walter, Peter J. ^{[2
]}

Herscovitch, Peter ^{[3
]}

Chen, Kong Y. ^{[1
]}

Cypess, Aaron M. ^{[1
]}

机构：

[1] NIDDK, Diabet Endocrinol & Obes Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA

[2] NIDDK, Clin Mass Spectrometry Core, NIH, Bethesda, MD 20892 USA

[3] NIH, Dept Positron Emiss Tomog, Bldg 10, Bethesda, MD 20892 USA

[4] BERG, Framingham, MA USA

来源：

DIABETES | 2018年 / 67卷 / 10期

关键词：

MYOCARDIAL OXYGEN-CONSUMPTION; OVERACTIVE BLADDER; BROWN FAT; BETA(3)-ADRENOCEPTOR AGONIST; FUNCTIONAL-CHARACTERIZATION; ENERGY HOMEOSTASIS; GENE-EXPRESSION; ADULT HUMANS; DOUBLE-BLIND; COLD;

D O I：

10.2337/db18-0462

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

beta 3-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 beta 3-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 beta 3-AR agonist mirabegron. There was a more-than-dose-proportional increase in BAT metabolic activity as measured by [F-18]-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 beta 3-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 beta 3-AR agonists to treat obesity-related complications.

引用

页码：2113 / 2125

页数：13

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