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

Please always quote using this URN: urn:nbn:de:bvb:20-opus-143127
  • 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 andObesity 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.show moreshow less

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Metadaten
Author: Linda S. Hoffmann, Jennifer Etzrodt, Lena Willkomm, Abhishek Sanyal, Ludger Scheja, Alexander W. C. Fischer, Johannes-Peter Stasch, Wilhelm Bloch, Andreas Friebe, Joerg Heeren, Alexander Pfeifer
URN:urn:nbn:de:bvb:20-opus-143127
Document Type:Journal article
Faculties:Medizinische Fakultät / Physiologisches Institut
Language:English
Parent Title (English):Nature Communications
Year of Completion:2015
Volume:6
Issue:7235
Source:Nature Communications 6:7235 (2015). DOI: 10.1038/ncomms8235
DOI:https://doi.org/10.1038/ncomms8235
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:beige adipocytes; cGMP; decompensated heart failure; erectile dysfunction; fat development; mitochondrial biogenesis; nitric oxide; pulmonary hypertension; riociguat; white
Release Date:2017/11/02
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International