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cGMP and Brown Adipose Tissue

  • Chapter
Metabolic Control

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 233))

Abstract

The second messenger cyclic guanosine monophosphate (cGMP) is a key mediator in physiological processes such as vascular tone, and its essential involvement in pathways regulating metabolism has been recognized in recent years. Here, we focus on the fundamental role of cGMP in brown adipose tissue (BAT) differentiation and function. In contrast to white adipose tissue (WAT), which stores energy in the form of lipids, BAT consumes energy stored in lipids to generate heat. This so-called non-shivering thermogenesis takes place in BAT mitochondria, which express the specific uncoupling protein 1 (UCP1). The energy combusting properties of BAT render it a promising target in antiobesity strategies in which BAT could burn the surplus energy that has accumulated in obese and overweight individuals. cGMP is generated by guanylyl cyclases upon activation by nitric oxide or natriuretic peptides. It affects several downstream molecules including cGMP-receptor proteins such as cGMP-dependent protein kinase and is degraded by phosphodiesterases. The cGMP pathway contains several signaling molecules that can increase cGMP signaling, resulting in activation and recruitment of brown adipocytes, and hence can enhance the energy combusting features of BAT. In this review we highlight recent results showing the physiological significance of cGMP signaling in BAT, as well as pharmacological options targeting cGMP signaling that bear a high potential to become BAT-centered therapies for the treatment of obesity.

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Authors and Affiliations

  1. Institute of Pharmacology and Toxicology, University Hospital, University of Bonn, 53127, Bonn, Germany

    Linda S. Hoffmann & Alexander Pfeifer

  2. Cardiovascular and Metabolic Diseases, Drug Discovery Unit, Takeda Pharmaceuticals, San Diego, CA, 92121, USA

    Christopher J. Larson

  3. NRW International Graduate Research School Biotech PHARMA, Bonn, Germany

    Alexander Pfeifer

  4. PharmaCenter, University of Bonn, 53127, Bonn, Germany

    Alexander Pfeifer

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  1. Linda S. Hoffmann
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  2. Christopher J. Larson
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  3. Alexander Pfeifer
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Correspondence to Alexander Pfeifer .

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Editors and Affiliations

  1. Helmholtz Center Munich, and Heidelberg University Hospital, Professor and Director, Institute for Diabetes and Cancer IDC, and Joint Heidelberg-IDC Translational Diabetes Program, Neuherberg, Germany

    Stephan Herzig

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Hoffmann, L.S., Larson, C.J., Pfeifer, A. (2015). cGMP and Brown Adipose Tissue. In: Herzig, S. (eds) Metabolic Control. Handbook of Experimental Pharmacology, vol 233. Springer, Cham. https://doi.org/10.1007/164_2015_3

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