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

Research output: Contribution to journalJournal articlesResearchpeer-review

Authors

  • Thorsten Gnad
  • Gemma Navarro
  • Minna Lahesmaa
  • Laia Reverte-Salisa
  • Francesca Copperi
  • Arnau Cordomi
  • Jennifer Naumann
  • Aileen Hochhäuser
  • Saskia Haufs-Brusberg
  • Daniela Wenzel
  • Frank Suhr
  • Naja Zenius Jespersen
  • Camilla Scheele
  • Volodymyr Tsvilovskyy
  • Joern Rittweger
  • Christian Dani
  • Mathias Kranz
  • Winnie Deuther-Conrad
  • Holger K Eltzschig
  • Tarja Niemi
  • Markku Taittonen
  • Peter Brust
  • Pirjo Nuutila
  • Leonardo Pardo
  • Bernd K Fleischmann
  • Matthias Blüher
  • Rafael Franco
  • Kirsi A Virtanen
  • Alexander Pfeifer

Research units

Details

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.

Original languageEnglish
JournalCell metabolism
Volume32
Issue number1
Pages (from-to)56-70.e7
Number of pages15
ISSN1550-4131
DOIs
Publication statusPublished - 07.07.2020

ID: 5350189

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