| Literature DB >> 32589947 |
Thorsten Gnad1, Gemma Navarro2, Minna Lahesmaa3, Laia Reverte-Salisa1, Francesca Copperi1, Arnau Cordomi4, Jennifer Naumann1, Aileen Hochhäuser1, Saskia Haufs-Brusberg1, Daniela Wenzel5, Frank Suhr6, Naja Zenius Jespersen7, Camilla Scheele8, Volodymyr Tsvilovskyy9, Christian Brinkmann10, Joern Rittweger11, Christian Dani12, Mathias Kranz13, Winnie Deuther-Conrad13, Holger K Eltzschig14, Tarja Niemi15, Markku Taittonen16, Peter Brust13, Pirjo Nuutila3, Leonardo Pardo4, Bernd K Fleischmann17, Matthias Blüher18, Rafael Franco2, Wilhelm Bloch19, Kirsi A Virtanen20, Alexander Pfeifer21.
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.Entities:
Keywords: GPCR; adenosine; adenosine receptor A2B; aging; brown adipose tissue; browning; energy metabolism; muscle; obesity; sarcopenia
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Year: 2020 PMID： 32589947 PMCID： PMC7437516 DOI： 10.1016/j.cmet.2020.06.006
Source DB: PubMed Journal: Cell Metab ISSN： 1550-4131 Impact factor: 27.287