TY  - JOUR
A1  - Hoffmann, Linda S.
A1  - Etzrodt, Jennifer
A1  - Willkomm, Lena
A1  - Sanyal, Abhishek
A1  - Scheja, Ludger
A1  - Fischer, Alexander W. C.
A1  - Stasch, Johannes-Peter
A1  - Bloch, Wilhelm
A1  - Friebe, Andreas
A1  - Heeren, Joerg
A1  - Pfeifer, Alexander
T1  - Stimulation of soluble guanylyl cyclase protects against obesity by recruiting brown adipose tissue
JF  - Nature Communications
N2  - 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.
KW  - decompensated heart failure
KW  - mitochondrial biogenesis
KW  - pulmonary hypertension
KW  - nitric oxide
KW  - erectile dysfunction
KW  - beige adipocytes
KW  - fat development
KW  - cGMP
KW  - riociguat
KW  - white
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-143127
VL  - 6
IS  - 7235
ER  -