A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä
Regulation of human brown adipose tissue by adenosine and A2A receptors – studies with [15O]H2O and [11C]TMSX PET/CT




Julkaisun tekijät: Minna Lahesmaa, Vesa Oikonen, Semi Helin, Pauliina Luoto, Mueez U Din, Alexander Pfeifer, Pirjo Nuutila, Kirsi A. Virtanen
Kustantaja: Springer Berlin Heidelberg
Julkaisuvuosi: 2019
Journal: European Journal of Nuclear Medicine and Molecular Imaging
Tietokannassa oleva lehden nimi: European Journal of Nuclear Medicine and Molecular Imaging
Volyymi: 46
Julkaisunumero: 3
ISSN: 1619-7070
eISSN: 1619-7089

Tiivistelmä

Purpose

Brown
adipose tissue (BAT) has emerged as a potential target to combat
obesity and diabetes, but novel strategies to activate BAT are needed.
Adenosine and A2A receptor (A2AR) agonism activate BAT in
rodents, and endogenous adenosine is released locally in BAT as a
by-product of noradrenaline, but physiological data from humans is
lacking. The purpose of this pilot study was to investigate the effects
of exogenous adenosine on human BAT perfusion, and to determine the
density of A2ARs in human BAT in vivo for the first time, using PET/CT
imaging.

Methods

Healthy, lean men (n = 10)
participated in PET/CT imaging with two radioligands. Perfusion of BAT,
white adipose tissue (WAT) and muscle was quantified with [15O]H2O
at baseline, during cold exposure and during intravenous administration
of adenosine. A2AR density of the tissues was quantified with [11C]TMSX at baseline and during cold exposure.

Results

Adenosine
increased the perfusion of BAT even more than cold exposure (baseline
8.3 ± 4.5, cold 19.6 ± 9.3, adenosine 28.6 ± 7.9 ml/100 g/min, p < 0.01). Distribution volume of [11C]TMSX in BAT was significantly lower during cold exposure compared to baseline. In cold, low [11C]TMSX binding coincided with high concentrations of noradrenaline.

Conclusions

Adenosine
administration caused a maximal perfusion effect in human
supraclavicular BAT, indicating increased oxidative metabolism. Cold
exposure increased noradrenaline concentrations and decreased the
density of A2AR available for radioligand binding in BAT, suggesting
augmented release of endogenous adenosine. Our results show that
adenosine and A2AR are relevant for activation of human BAT, and A2AR
provides a future target for enhancing BAT metabolism.


Ladattava julkaisu

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Last updated on 2019-19-02 at 17:57