Adenosine/A2B Receptor Signaling Ameliorates the Effects of Aging and Counteracts Obesity
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Adenosine/A2B Receptor Signaling Ameliorates the Effects of Aging and Counteracts Obesity. / Gnad, Thorsten; Navarro, Gemma; Lahesmaa, Minna; Reverte-Salisa, Laia; Copperi, Francesca; Cordomi, Arnau; Naumann, Jennifer; Hochhaeuser, Aileen; Haufs-Brusberg, Saskia; Wenzel, Daniela; Suhr, Frank; Jespersen, Naja Zenius; Scheele, Camilla; Tsvilovskyy, Volodymyr; Brinkmann, Christian; Rittweger, Joern; Dani, Christian; 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, Kirsi A.; Pfeifer, Alexander.
In: Cell Metabolism, Vol. 32, No. 1, 2020, p. 56-70.e7.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Adenosine/A2B Receptor Signaling Ameliorates the Effects of Aging and Counteracts Obesity
AU - Gnad, Thorsten
AU - Navarro, Gemma
AU - Lahesmaa, Minna
AU - Reverte-Salisa, Laia
AU - Copperi, Francesca
AU - Cordomi, Arnau
AU - Naumann, Jennifer
AU - Hochhaeuser, Aileen
AU - Haufs-Brusberg, Saskia
AU - Wenzel, Daniela
AU - Suhr, Frank
AU - Jespersen, Naja Zenius
AU - Scheele, Camilla
AU - Tsvilovskyy, Volodymyr
AU - Brinkmann, Christian
AU - Rittweger, Joern
AU - Dani, Christian
AU - Kranz, Mathias
AU - Deuther-Conrad, Winnie
AU - Eltzschig, Holger K.
AU - Niemi, Tarja
AU - Taittonen, Markku
AU - Brust, Peter
AU - Nuutila, Pirjo
AU - Pardo, Leonardo
AU - Fleischmann, Bernd K.
AU - Blueher, Matthias
AU - Franco, Rafael
AU - Bloch, Wilhelm
AU - Virtanen, Kirsi A.
AU - Pfeifer, Alexander
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
KW - BROWN ADIPOSE-TISSUE
KW - SKELETAL-MUSCLE
KW - FUNCTIONAL-CHARACTERIZATION
KW - INTERNATIONAL UNION
KW - SARCOPENIC OBESITY
KW - BEIGE ADIPOCYTES
KW - DOPAMINE D-1
KW - STEM-CELLS
KW - CROSS-TALK
KW - FAT
U2 - 10.1016/j.cmet.2020.06.006
DO - 10.1016/j.cmet.2020.06.006
M3 - Journal article
C2 - 32589947
VL - 32
SP - 56-70.e7
JO - Cell Metabolism
JF - Cell Metabolism
SN - 1550-4131
IS - 1
ER -
ID: 250120484