Adenosine/A2B Receptor Signaling Ameliorates the Effects of Aging and Counteracts Obesity

Gnad, Thorsten and Navarro, Gemma and Lahesmaa, Minna and Reverte-Salisa, Laia and Copperi, Francesca and Cordomi, Arnau and Naumann, Jennifer and Hochhäuser, Aileen and Haufs-Brusberg, Saskia and Wenzel, Daniela and Suhr, Frank and Jespersen, Naja Zenius and Scheele, Camilla and Tsvilovskyy, Volodymyr and Brinkmann, Christian and Rittweger, Jörn and Dani, Christian and Kranz, Mathias and Deuther-Conrad, Winnie and Eltzschig, Holger K. and Niemi, Tarja and Taittonen, Markku and Brust, Peter and Nuutila, Pirjo and Pardo, Leonardo and Fleischmann, Bernd K. and Blüher, Matthias and Franco, Rafael and Bloch, Wilhelm and Virtanen, Kirsi A. and Pfeifer, Alexander (2020) Adenosine/A2B Receptor Signaling Ameliorates the Effects of Aging and Counteracts Obesity. Cell Metabolism, 32 (1), 56-70.e7. Cell Press. doi: 10.1016/j.cmet.2020.06.006. ISSN 1550-4131.

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Official URL: https://www.sciencedirect.com/science/article/abs/pii/S1550413120303077?via%3Dihub

Abstract

The combination of aging populations with the obesity pandemic results in an alarming rise in non-communicable diseases. Here, we show that the enigmatic adenosine A2B receptor (A2B) is abundantly expressed in skeletal muscle (SKM) as well as brown adipose tissue (BAT) and might be targeted to counteract age-related muscle atrophy (sarcopenia) as well as obesity. Mice with SKM-specific deletion of A2B exhibited sarcopenia, diminished muscle strength, and reduced energy expenditure (EE), whereas pharmacological A2B activation counteracted these processes. Adipose tissue-specific ablation of A2B exacerbated age-related processes and reduced BAT EE, whereas A2B stimulation ameliorated obesity. In humans, A2B expression correlated with EE in SKM, BAT activity, and abundance of thermogenic adipocytes in white fat. Moreover, A2B agonist treatment increased EE from human adipocytes, myocytes, and muscle explants. Mechanistically, A2B forms heterodimers required for adenosine signaling. Overall, adenosine/A2B signaling links muscle and BAT and has both anti-aging and anti–obesity potential.

Item URL in elib:

https://elib.dlr.de/135819/

Document Type:

Article

Title:

Adenosine/A2B Receptor Signaling Ameliorates the Effects of Aging and Counteracts Obesity

Authors:

Authors	Institution or Email of Authors	Author's ORCID iD	ORCID Put Code
Gnad, Thorsten	Institute of Pharmacology and Toxicology, University Hospital, University of Bonn, 53127 Bonn, Germany	UNSPECIFIED	UNSPECIFIED
Navarro, Gemma	Department of Biochemistry and Molecular Biomedicine, Faculty of Biology, University of Barcelona, Barcelona, Spain	UNSPECIFIED	UNSPECIFIED
Lahesmaa, Minna	Turku PET Centre, Turku University Hospital, University of Turku, Turku, Finland	UNSPECIFIED	UNSPECIFIED
Reverte-Salisa, Laia	Institute of Pharmacology and Toxicology, University Hospital, University of Bonn, 53127 Bonn, Germany	UNSPECIFIED	UNSPECIFIED
Copperi, Francesca	Institute of Pharmacology and Toxicology, University Hospital, University of Bonn, 53127 Bonn, Germany	UNSPECIFIED	UNSPECIFIED
Cordomi, Arnau	Laboratory of Computational Medicine, Universitat Autonoma de Barcelona, Barcelona, Spain	UNSPECIFIED	UNSPECIFIED
Naumann, Jennifer	Institute of Pharmacology and Toxicology, University Hospital, University of Bonn, 53127 Bonn, Germany	UNSPECIFIED	UNSPECIFIED
Hochhäuser, Aileen	Institute of Pharmacology and Toxicology, University Hospital, University of Bonn, 53127 Bonn, Germany	UNSPECIFIED	UNSPECIFIED
Haufs-Brusberg, Saskia	Institute of Pharmacology and Toxicology, University Hospital, University of Bonn, 53127 Bonn, Germany	UNSPECIFIED	UNSPECIFIED
Wenzel, Daniela	UNSPECIFIED	UNSPECIFIED	UNSPECIFIED
Suhr, Frank	German Sport University Cologne	UNSPECIFIED	UNSPECIFIED
Jespersen, Naja Zenius	Centre for Physical Activity Research, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark	UNSPECIFIED	UNSPECIFIED
Scheele, Camilla	Centre for Physical Activity Research, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark	UNSPECIFIED	UNSPECIFIED
Tsvilovskyy, Volodymyr	Institute of Pharmacology, Ruprecht-Karls University, Heidelberg, Germany	UNSPECIFIED	UNSPECIFIED
Brinkmann, Christian	Department of Preventive and Rehabilitative Sport Medicine, German Sport University Cologne, Cologne, Germany	UNSPECIFIED	UNSPECIFIED
Rittweger, Jörn	UNSPECIFIED	https://orcid.org/0000-0002-2223-8963	UNSPECIFIED
Dani, Christian	Université Côte d’Azur, CNRS, Inserm, iBV, Faculté de Médecine, 06107 Nice Cedex 2, France	UNSPECIFIED	UNSPECIFIED
Kranz, Mathias	Helmholtz-Zentrum Dresden – Rossendorf, Institute of Radiopharmaceutical Cancer Research, Research Site Leipzig, Leipzig, Germany	UNSPECIFIED	UNSPECIFIED
Deuther-Conrad, Winnie	Helmholtz-Zentrum Dresden – Rossendorf, Institute of Radiopharmaceutical Cancer Research, Research Site Leipzig, Leipzig, Germany	UNSPECIFIED	UNSPECIFIED
Eltzschig, Holger K.	Department of Anesthesiology, University of Texas Health Science Center at Houston, McGovern Medical School, Houston, TX, USA	UNSPECIFIED	UNSPECIFIED
Niemi, Tarja	Department of Plastic and General Surgery, Turku University Hospital, Turku, Finland	UNSPECIFIED	UNSPECIFIED
Taittonen, Markku	Department of Anesthesiology, Turku University Hospital, Turku, Finland	UNSPECIFIED	UNSPECIFIED
Brust, Peter	Helmholtz-Zentrum Dresden – Rossendorf, Institute of Radiopharmaceutical Cancer Research, Research Site Leipzig, Leipzig, Germany	UNSPECIFIED	UNSPECIFIED
Nuutila, Pirjo	Turku PET Centre, Turku University Hospital, University of Turku, Turku, Finland	UNSPECIFIED	UNSPECIFIED
Pardo, Leonardo	Laboratory of Computational Medicine, Universitat Autonoma de Barcelona, Barcelona, Spain	UNSPECIFIED	UNSPECIFIED
Fleischmann, Bernd K.	Institute of Physiology I, Life&Brain Center, Medical Faculty, University of Bonn, 53105 Bonn, Germany	UNSPECIFIED	UNSPECIFIED
Blüher, Matthias	Department of Medicine, University of Leipzig, Leipzig, Germany	UNSPECIFIED	UNSPECIFIED
Franco, Rafael	Department of Biochemistry and Molecular Biomedicine, Faculty of Biology, University of Barcelona, Barcelona, Spain	UNSPECIFIED	UNSPECIFIED
Bloch, Wilhelm	German Sport University Cologne	UNSPECIFIED	UNSPECIFIED
Virtanen, Kirsi A.	Turku PET Centre, Turku University Hospital, University of Turku, Turku, Finland	UNSPECIFIED	UNSPECIFIED
Pfeifer, Alexander	Institute of Pharmacology and Toxicology, University Hospital, University of Bonn, 53127 Bonn, Germany	UNSPECIFIED	UNSPECIFIED

Date:

25 June 2020

Journal or Publication Title:

Cell Metabolism

Refereed publication:

Yes

Open Access:

Yes

Gold Open Access:

In SCOPUS:

Yes

In ISI Web of Science:

Yes

Volume:

DOI:

10.1016/j.cmet.2020.06.006

Page Range:

56-70.e7

Publisher:

Cell Press

ISSN:

1550-4131

Status:

Published

Keywords:

aging, energy metabolism, sarcopenia, muscle, brown adipose tissue, GPCR, adenosine, adenosine receptor A2B, obesity, browning

HGF - Research field:

Aeronautics, Space and Transport

HGF - Program:

Space

HGF - Program Themes:

Research under Space Conditions

DLR - Research area:

Raumfahrt

DLR - Program:

R FR - Research under Space Conditions

DLR - Research theme (Project):

R - Vorhaben Systemphysiologie (old)

Location:

Köln-Porz

Institutes and Institutions:

Institute of Aerospace Medicine > Muscle and Bone Metabolism

Deposited By:

Arndt, Carina

Deposited On:

27 Aug 2020 14:03

Last Modified:

16 Jul 2021 09:24

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