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

Authors
  • Gnad, Thorsten1
  • Navarro, Gemma2
  • Lahesmaa, Minna3
  • Reverte-Salisa, Laia1
  • Copperi, Francesca1
  • Cordomi, Arnau4
  • Naumann, Jennifer1
  • Hochhäuser, Aileen1
  • Haufs-Brusberg, Saskia1
  • Wenzel, Daniela5
  • Suhr, Frank6
  • Jespersen, Naja Zenius7
  • Scheele, Camilla8
  • Tsvilovskyy, Volodymyr9
  • Brinkmann, Christian10
  • Rittweger, Joern11
  • Dani, Christian12
  • Kranz, Mathias13
  • Deuther-Conrad, Winnie13
  • Eltzschig, Holger K14
  • And 11 more
  • 1 Institute of Pharmacology and Toxicology, University Hospital, University of Bonn, 53127 Bonn, Germany. , (Germany)
  • 2 Department of Biochemistry and Molecular Biomedicine, Faculty of Biology, University of Barcelona, Barcelona, Spain; Centro de Investigación en Red, Enfermedades Neurodegenerativas (CiberNed), Instituto de Salud Carlos III, Madrid, Spain. , (Spain)
  • 3 Turku PET Centre, Turku University Hospital, University of Turku, Turku, Finland. , (Finland)
  • 4 Laboratory of Computational Medicine, Universitat Autonoma de Barcelona, Barcelona, Spain. , (Spain)
  • 5 Institute of Physiology I, Life&Brain Center, Medical Faculty, University of Bonn, 53105 Bonn, Germany; Department of Systems Physiology, Medical Faculty, Ruhr University Bochum, Bochum, Germany. , (Germany)
  • 6 Molecular and Cellular Sport Medicine, German Sport University Cologne, Cologne, Germany; Exercise Physiology Research Group, Biomedical Sciences Group, KU Leuven, Leuven, Belgium. , (Belgium)
  • 7 Centre for Physical Activity Research, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. , (Denmark)
  • 8 Centre for Physical Activity Research, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. , (Denmark)
  • 9 Institute of Pharmacology, Ruprecht-Karls University, Heidelberg, Germany. , (Germany)
  • 10 Department of Preventive and Rehabilitative Sport Medicine, German Sport University Cologne, Cologne, Germany. , (Germany)
  • 11 Department of Muscle and Bone Metabolism, German Aerospace Center (DLR), Institute of Aerospace Medicine, Cologne, Germany. , (Germany)
  • 12 Université Côte d'Azur, CNRS, Inserm, iBV, Faculté de Médecine, 06107 Nice Cedex 2, France. , (France)
  • 13 Helmholtz-Zentrum Dresden - Rossendorf, Institute of Radiopharmaceutical Cancer Research, Research Site Leipzig, Leipzig, Germany. , (Germany)
  • 14 Department of Anesthesiology, University of Texas Health Science Center at Houston, McGovern Medical School, Houston, TX, USA.
  • 15 Department of Plastic and General Surgery, Turku University Hospital, Turku, Finland. , (Finland)
  • 16 Department of Anesthesiology, Turku University Hospital, Turku, Finland. , (Finland)
  • 17 Institute of Physiology I, Life&Brain Center, Medical Faculty, University of Bonn, 53105 Bonn, Germany. , (Germany)
  • 18 Department of Medicine, University of Leipzig, Leipzig, Germany. , (Germany)
  • 19 Molecular and Cellular Sport Medicine, German Sport University Cologne, Cologne, Germany. , (Germany)
  • 20 Turku PET Centre, Turku University Hospital, University of Turku, Turku, Finland; Institute of Public Health and Clinical Nutrition, University of Eastern Finland (UEF), Kuopio, Finland. , (Finland)
  • 21 Institute of Pharmacology and Toxicology, University Hospital, University of Bonn, 53127 Bonn, Germany. Electronic address: [email protected] , (Germany)
Type
Published Article
Journal
Cell metabolism
Publication Date
Jul 07, 2020
Volume
32
Issue
1
Identifiers
DOI: 10.1016/j.cmet.2020.06.006
PMID: 32589947
Source
Medline
Keywords
Language
English
License
Unknown

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. Copyright © 2020 Elsevier Inc. All rights reserved.

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