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

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; 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

doi:10.1016/j.cmet.2020.06.006

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

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, Christian Brinkmann, Joern Rittweger, Christian Dani, Mathias Kranz, Winnie Deuther-Conrad, Holger K EltzschigTarja Niemi, Markku Taittonen, Peter Brust, Pirjo Nuutila, Leonardo Pardo, Bernd K Fleischmann, Matthias Blüher, Rafael Franco, Wilhelm Bloch, Kirsi A Virtanen, Alexander Pfeifer

Publikation: Beitrag in Fachzeitschrift › Zeitschriftenaufsätze › Forschung › Begutachtung

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.

Originalsprache	Englisch
Zeitschrift	Cell metabolism
Jahrgang	32
Ausgabenummer	1
Seiten (von - bis)	56-70.e7
Seitenumfang	15
ISSN	1550-4131
DOIs	https://doi.org/10.1016/j.cmet.2020.06.006
Publikationsstatus	Veröffentlicht - 07.07.2020

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10.1016/j.cmet.2020.06.006

Zitation

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, N. Z., Scheele, C., Tsvilovskyy, V., Brinkmann, C., Rittweger, J., Dani, C., Kranz, M., Deuther-Conrad, W., ... Pfeifer, A. (2020). Adenosine/A2B Receptor Signaling Ameliorates the Effects of Aging and Counteracts Obesity. Cell metabolism, 32(1), 56-70.e7. https://doi.org/10.1016/j.cmet.2020.06.006

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title = "Adenosine/A2B Receptor Signaling Ameliorates the Effects of Aging and Counteracts Obesity",

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.",

author = "Thorsten Gnad and Gemma Navarro and Minna Lahesmaa and Laia Reverte-Salisa and Francesca Copperi and Arnau Cordomi and Jennifer Naumann and Aileen Hochh{\"a}user and Saskia Haufs-Brusberg and Daniela Wenzel and Frank Suhr and Jespersen, {Naja Zenius} and Camilla Scheele and Volodymyr Tsvilovskyy and Christian Brinkmann and Joern Rittweger and Christian Dani and Mathias Kranz and Winnie Deuther-Conrad and Eltzschig, {Holger K} and Tarja Niemi and Markku Taittonen and Peter Brust and Pirjo Nuutila and Leonardo Pardo and Fleischmann, {Bernd K} and Matthias Bl{\"u}her and Rafael Franco and Wilhelm Bloch and Virtanen, {Kirsi A} and Alexander Pfeifer",

year = "2020",

month = jul,

day = "7",

doi = "10.1016/j.cmet.2020.06.006",

language = "English",

volume = "32",

pages = "56--70.e7",

journal = "Cell metabolism",

issn = "1550-4131",

publisher = "Cell Press",

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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 metabolism, Jg. 32, Nr. 1, S. 56-70.e7. https://doi.org/10.1016/j.cmet.2020.06.006

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 - Hochhäuser, 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 - Blüher, Matthias

AU - Franco, Rafael

AU - Bloch, Wilhelm

AU - Virtanen, Kirsi A

AU - Pfeifer, Alexander

PY - 2020/7/7

Y1 - 2020/7/7

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.

UR - https://www.mendeley.com/catalogue/8d5122cc-a323-332f-a5c4-54da4f5520f1/

U2 - 10.1016/j.cmet.2020.06.006

DO - 10.1016/j.cmet.2020.06.006

M3 - Journal articles

C2 - 32589947

SN - 1550-4131

VL - 32

SP - 56-70.e7

JO - Cell metabolism

JF - Cell metabolism

IS - 1

ER -

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

Abstract

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