Title: Adenosine/A2B Receptor Signaling Ameliorates the Effects of Aging and Counteracts Obesity
Author: Thorsten Gnad, Gemma Navarro, Minna Lahesmaa, Laia Reverte-Salisa, Francesca Copperi, Arnau Cordomi, Jennifer Naumann, Aileen Hochhuser, Saskia Haufs-Brusberg, Daniela Wenzel, Frank Suhr, Naja Zenius Jespersen, Camilla Scheele, Volodymyr Tsvilovskyy, Christian Brinkmann, 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, Wilhelm Bloch, Kirsi A. Virtanen, Alexander Pfeifer
Abstract: The combination of aging populations with the obesity pandemic results in an alarmingrise in non-communicable diseases. Here, we show that the enigmatic adenosine A2Breceptor (A2B) is abundantly expressed in skeletal muscle (SKM) as well as brown adiposetissue (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, diminishedmuscle strength, and reduced energy expenditure (EE), whereas pharmacological A2Bactivation counteracted these processes. Adipose tissue-specific ablation of A2B exacerbatedage-related processes and reduced BAT EE, whereas A2B stimulation ameliorated obesity.In humans, A2B expression correlated with EE in SKM, BAT activity, and abundance ofthermogenic adipocytes in white fat. Moreover, A2B agonist treatment increased EEfrom human adipocytes, myocytes, and muscle explants. Mechanistically, A2B forms heterodimersrequired for adenosine signaling. Overall, adenosine/A2B signaling links muscle andBAT and has both anti-aging and anti–obesity potential.