To the top

Page Manager: Webmaster
Last update: 9/11/2012 3:13 PM

Tell a friend about this page
Print version

Adenosine activates brown… - University of Gothenburg, Sweden Till startsida
Sitemap
To content Read more about how we use cookies on gu.se

Adenosine activates brown adipose tissue and recruits beige adipocytes via A(2A) receptors

Journal article
Authors T. Gnad
S. Scheibler
I. von Kugelgen
C. Scheele
A. Kilic
A. Glode
L. S. Hoffmann
L. Reverte-Salisa
P. Horn
S. Mutlu
A. El-Tayeb
M. Kranz
W. Deuther-Conrad
P. Brust
Martin Lidell
Mattias J. Betz
Sven Enerbäck
J. Schrader
G. G. Yegutkin
C. E. Muller
A. Pfeifer
Published in Nature
Volume 516
Issue 7531
Pages 395-+
ISSN 0028-0836
Publication year 2014
Published at Institute of Biomedicine, Department of Medical and Clinical Genetics
Pages 395-+
Language en
Links dx.doi.org/10.1038/nature13816
Keywords FAT, MOUSE, NORADRENALINE, RESPIRATION, LIPOLYSIS, HUMANS, CELLS, ATP
Subject categories Cell and Molecular Biology

Abstract

Brown adipose tissue (BAT) is specialized in energy expenditure, making it a potential target for anti-obesity therapies(1-5). Following exposure to cold, BAT is activated by the sympathetic nervous system with concomitant release of catecholamines and activation of beta-adrenergic receptors(1-5). Because BAT therapies based on cold exposureor beta-adrenergic agonists are clinically not feasible, alternative strategies must be explored. Purinergic co-transmission might be involved in sympathetic control of BAT and previous studies reported inhibitory effects of the purinergic transmitter adenosine in BAT from hamster or rat(6-8). However, the role of adenosine in human BAT is unknown. Here we show that adenosine activates human and murine brown adipocytes at low nanomolar concentrations. Adenosine is released in BAT during stimulation of sympathetic nerves as well as from brown adipocytes. The adenosine A(2A) receptor is the most abundant adenosine receptor in human and murine BAT. Pharmacological blockade or genetic loss of A(2A) receptors in mice causes adecrease in BAT-dependent thermogenesis, whereas treatment with A(2A) agonists significantly increases energy expenditure. Moreover, pharmacological stimulation of A(2A) receptors or injection of lentiviral vectors expressing the A(2A) receptor into white fat induces brown-like cells-so-called beige adipocytes. Importantly, mice fed a high-fat diet and treated with an A(2A) agonist are leaner with improved glucose tolerance. Taken together, our results demonstrate that adenosine-A(2A) signalling plays an unexpected physiological role in sympathetic BAT activation and protects mice from diet-induced obesity. Those findings reveal new possibilities for developing novel obesity therapies.

Page Manager: Webmaster|Last update: 9/11/2012
Share:

The University of Gothenburg uses cookies to provide you with the best possible user experience. By continuing on this website, you approve of our use of cookies.  What are cookies?