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

Author

Listed:
  • 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
    Present address: Institute of Human Genetics, University Hospital, University of Cologne, D-50735 Cologne, Germany.)

  • Abhishek Sanyal

    (Institute of Pharmacology and Toxicology, University Hospital Bonn, University of Bonn
    Research Training Group 1873, 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
    Institute of Pharmacy, Martin Luther University Halle-Wittenberg)

  • 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
    Research Training Group 1873, University of Bonn
    PharmaCenter, University of Bonn)

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.

Suggested Citation

  • 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 Pfei, 2015. "Stimulation of soluble guanylyl cyclase protects against obesity by recruiting brown adipose tissue," Nature Communications, Nature, vol. 6(1), pages 1-9, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8235
    DOI: 10.1038/ncomms8235
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