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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:
AuthorsInstitution or Email of AuthorsAuthor's ORCID iD
Gnad, ThorstenInstitute of Pharmacology and Toxicology, University Hospital, University of Bonn, 53127 Bonn, GermanyUNSPECIFIED
Navarro, GemmaDepartment of Biochemistry and Molecular Biomedicine, Faculty of Biology, University of Barcelona, Barcelona, SpainUNSPECIFIED
Lahesmaa, MinnaTurku PET Centre, Turku University Hospital, University of Turku, Turku, FinlandUNSPECIFIED
Reverte-Salisa, LaiaInstitute of Pharmacology and Toxicology, University Hospital, University of Bonn, 53127 Bonn, GermanyUNSPECIFIED
Copperi, FrancescaInstitute of Pharmacology and Toxicology, University Hospital, University of Bonn, 53127 Bonn, GermanyUNSPECIFIED
Cordomi, ArnauLaboratory of Computational Medicine, Universitat Autonoma de Barcelona, Barcelona, SpainUNSPECIFIED
Naumann, JenniferInstitute of Pharmacology and Toxicology, University Hospital, University of Bonn, 53127 Bonn, GermanyUNSPECIFIED
Hochhäuser, AileenInstitute of Pharmacology and Toxicology, University Hospital, University of Bonn, 53127 Bonn, GermanyUNSPECIFIED
Haufs-Brusberg, SaskiaInstitute of Pharmacology and Toxicology, University Hospital, University of Bonn, 53127 Bonn, GermanyUNSPECIFIED
Wenzel, Danieladaniela.wenzel (at) dlr.deUNSPECIFIED
Suhr, FrankGerman Sport University CologneUNSPECIFIED
Jespersen, Naja ZeniusCentre for Physical Activity Research, Rigshospitalet, University of Copenhagen, Copenhagen, DenmarkUNSPECIFIED
Scheele, CamillaCentre for Physical Activity Research, Rigshospitalet, University of Copenhagen, Copenhagen, DenmarkUNSPECIFIED
Tsvilovskyy, VolodymyrInstitute of Pharmacology, Ruprecht-Karls University, Heidelberg, GermanyUNSPECIFIED
Brinkmann, ChristianDepartment of Preventive and Rehabilitative Sport Medicine, German Sport University Cologne, Cologne, GermanyUNSPECIFIED
Rittweger, JörnJoern.Rittweger (at) dlr.dehttps://orcid.org/0000-0002-2223-8963
Dani, ChristianUniversité Côte d’Azur, CNRS, Inserm, iBV, Faculté de Médecine, 06107 Nice Cedex 2, FranceUNSPECIFIED
Kranz, MathiasHelmholtz-Zentrum Dresden – Rossendorf, Institute of Radiopharmaceutical Cancer Research, Research Site Leipzig, Leipzig, GermanyUNSPECIFIED
Deuther-Conrad, WinnieHelmholtz-Zentrum Dresden – Rossendorf, Institute of Radiopharmaceutical Cancer Research, Research Site Leipzig, Leipzig, GermanyUNSPECIFIED
Eltzschig, Holger K.Department of Anesthesiology, University of Texas Health Science Center at Houston, McGovern Medical School, Houston, TX, USAUNSPECIFIED
Niemi, TarjaDepartment of Plastic and General Surgery, Turku University Hospital, Turku, FinlandUNSPECIFIED
Taittonen, MarkkuDepartment of Anesthesiology, Turku University Hospital, Turku, FinlandUNSPECIFIED
Brust, PeterHelmholtz-Zentrum Dresden – Rossendorf, Institute of Radiopharmaceutical Cancer Research, Research Site Leipzig, Leipzig, GermanyUNSPECIFIED
Nuutila, PirjoTurku PET Centre, Turku University Hospital, University of Turku, Turku, FinlandUNSPECIFIED
Pardo, LeonardoLaboratory of Computational Medicine, Universitat Autonoma de Barcelona, Barcelona, SpainUNSPECIFIED
Fleischmann, Bernd K.Institute of Physiology I, Life&Brain Center, Medical Faculty, University of Bonn, 53105 Bonn, GermanyUNSPECIFIED
Blüher, MatthiasDepartment of Medicine, University of Leipzig, Leipzig, GermanyUNSPECIFIED
Franco, RafaelDepartment of Biochemistry and Molecular Biomedicine, Faculty of Biology, University of Barcelona, Barcelona, SpainUNSPECIFIED
Bloch, WilhelmGerman Sport University CologneUNSPECIFIED
Virtanen, Kirsi A.Turku PET Centre, Turku University Hospital, University of Turku, Turku, FinlandUNSPECIFIED
Pfeifer, AlexanderInstitute of Pharmacology and Toxicology, University Hospital, University of Bonn, 53127 Bonn, GermanyUNSPECIFIED
Date:25 June 2020
Journal or Publication Title:Cell Metabolism
Refereed publication:Yes
Open Access:No
Gold Open Access:No
In SCOPUS:Yes
In ISI Web of Science:Yes
Volume:32
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:30 Sep 2020 09:27

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