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

Linda S. Hoffmann, Jennifer Etzrodt, Lena Willkomm, Abhishek Sanyal, Ludger Scheja, Alexander W.C. Fischer, Johannes-Peter Stasch, Wilhelm Bloch, Andreas Friebe, Joerg Heeren and Alexander Pfeifer ()
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Linda S. Hoffmann: Institute of Pharmacology and Toxicology, University Hospital Bonn, University of Bonn
Jennifer Etzrodt: Institute of Pharmacology and Toxicology, University Hospital Bonn, University of Bonn
Lena Willkomm: German Sport University Cologne, Institute of Cardiovascular Research and Sports Medicine
Abhishek Sanyal: Institute of Pharmacology and Toxicology, University Hospital Bonn, University of Bonn
Ludger Scheja: University Medical Center Hamburg-Eppendorf
Alexander W.C. Fischer: University Medical Center Hamburg-Eppendorf
Johannes-Peter Stasch: Bayer Pharma AG
Wilhelm Bloch: German Sport University Cologne, Institute of Cardiovascular Research and Sports Medicine
Andreas Friebe: Institute of Physiology, Martin Luther University Würzburg
Joerg Heeren: University Medical Center Hamburg-Eppendorf
Alexander Pfeifer: Institute of Pharmacology and Toxicology, University Hospital Bonn, University of Bonn

Nature Communications, 2015, vol. 6, issue 1, 1-9

Abstract: Abstract 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 β1-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.

Date: 2015
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DOI: 10.1038/ncomms8235

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