Adenosine/A2B Receptor Signaling Ameliorates the Effects of Aging and Counteracts Obesity.
GPCR
adenosine
adenosine receptor A2B
aging
brown adipose tissue
browning
energy metabolism
muscle
obesity
sarcopenia
Journal
Cell metabolism
ISSN: 1932-7420
Titre abrégé: Cell Metab
Pays: United States
ID NLM: 101233170
Informations de publication
Date de publication:
07 07 2020
07 07 2020
Historique:
received:
01
08
2019
revised:
15
03
2020
accepted:
08
06
2020
pubmed:
27
6
2020
medline:
10
11
2021
entrez:
27
6
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32589947
pii: S1550-4131(20)30307-7
doi: 10.1016/j.cmet.2020.06.006
pmc: PMC7437516
mid: NIHMS1607842
pii:
doi:
Substances chimiques
Receptor, Adenosine A2B
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
56-70.e7Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK109574
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK122796
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL133900
Pays : United States
Commentaires et corrections
Type : CommentIn
Type : ErratumIn
Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests T.G., L.R.-S., F.C., D.W., J.N., A.H., S.H.-B., B.K.F., and A.P. have filed an application for patenting A2B agonist treatment of musculoskeletal disorders.
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