Gnad 2020 Cell Metab
|Gnad T, Navarro G, Lahesmaa M, Reverte-Salisa L, Copperi F, Cordomi A, Naumann J, Hochhäuser A, Haufs-Brusberg S, Wenzel D, Suhr F, Jespersen NZ, Scheele C, Tsvilovskyy V, Brinkmann C, Rittweger J, Dani C, Kranz M, Deuther-Conrad W, Eltzschig HK, Niemi T, Taittonen M, Brust P, Nuutila P, Pardo L, Fleischmann BK, Blüher M, Franco R, Bloch W, Virtanen KA, Pfeifer A (2020) Adenosine/A2B receptor signaling ameliorates the effects of aging and counteracts obesity. Cell Metab 32:56-70.e7.|
Gnad Thorsten, Navarro Gemma, Lahesmaa Minna, Reverte-Salisa Laia, Copperi Francesca, Cordomi Arnau, Naumann Jennifer, Hochhäuser Aileen, Haufs-Brusberg Saskia, Wenzel Daniela, Suhr Frank, Jespersen Naja Zenius, Scheele Camilla, Tsvilovskyy Volodymyr, Brinkmann Christian, Rittweger Joern, Dani Crhsitian, Kranz Mathias, Deuther-Conrad Winnie, Eltzschig Holger K, Niemi Tarja, Taittonen Markku, Brust Peter, Nuutila Pirjo, Pardo Leonardo, Fleischmann Bernd K, Blueher Matthias, Franco Rafael, Bloch Wilhelm, Virtanen Kirisi A, Pfeifer Alexander (2020) Cell Metab
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.
• Keywords: GPCR, Adenosine, Adenosine receptor A2B, Aging, Brown adipose tissue, Browning, Energy metabolism, Muscle, Obesity, Sarcopenia • Bioblast editor: Plangger M • O2k-Network Lab: DE Bonn Pfeifer A
Labels: MiParea: Respiration Pathology: Aging;senescence, Obesity
Organism: Mouse Tissue;cell: Skeletal muscle Preparation: Permeabilized tissue
Coupling state: LEAK, OXPHOS, ET Pathway: N, S HRR: Oxygraph-2k