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.…
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 |
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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): | CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International |