Stimulation of soluble guanylyl cyclase protects against obesity by recruiting brown adipose tissue

被引:80
作者
Hoffmann, Linda S. [1 ]
Etzrodt, Jennifer [1 ]
Willkomm, Lena [2 ]
Sanyal, Abhishek [1 ,3 ]
Scheja, Ludger [4 ]
Fischer, Alexander W. C. [4 ]
Stasch, Johannes-Peter [5 ,6 ]
Bloch, Wilhelm [2 ]
Friebe, Andreas [7 ]
Heeren, Joerg [4 ]
Pfeifer, Alexander [1 ,3 ,8 ]
机构
[1] Univ Bonn, Univ Hosp Bonn, Inst Pharmacol & Toxicol, D-53105 Bonn, Germany
[2] German Sport Univ Cologne, Inst Cardiovasc Res & Sports Med, Dept Mol & Cellular Sports Med, D-50735 Cologne, Germany
[3] Univ Bonn, Res Training Grp 1873, D-53127 Bonn, Germany
[4] Univ Med Ctr Hamburg Eppendorf, Dept Biochem & Mol Cell Biol, D-20246 Hamburg, Germany
[5] Bayer Pharma AG, D-42113 Wuppertal, Germany
[6] Univ Halle Wittenberg, Inst Pharm, D-06120 Halle, Germany
[7] Univ Wurzburg, Inst Physiol, D-97070 Wurzburg, Germany
[8] Univ Bonn, PharmaCtr, D-53119 Bonn, Germany
来源
NATURE COMMUNICATIONS | 2015年 / 6卷
关键词
MITOCHONDRIAL BIOGENESIS; BEIGE ADIPOCYTES; FAT DEVELOPMENT; RIOCIGUAT; WHITE; RISK; DIFFERENTIATION; DYSFUNCTION; METABOLISM; NESIRITIDE;
D O I
10.1038/ncomms8235
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Obesity is characterized by a positive energy balance and expansion of white adipose tissue (WAT). In contrast, brown adipose tissue (BAT) combusts energy to produce heat. Here we show that a small molecule stimulator (BAY 41-8543) of soluble guanylyl cyclase (sGC), which produces the second messenger cyclic GMP (cGMP), protects against diet-induced weight gain, induces weight loss in established obesity, and also improves the diabetic phenotype. Mechanistically, the haeme-dependent sGC stimulator BAY 41-8543 enhances lipid uptake into BAT and increases whole-body energy expenditure, whereas ablation of the haeme-containing beta(1)-subunit of sGC severely impairs BAT function. Notably, the sGC stimulator enhances differentiation of human brown adipocytes as well as induces 'browning' of primary white adipocytes. Taken together, our data suggest that sGC is a potential pharmacological target for the treatment of obesity and its comorbidities.
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页数:9
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