Key result
Intravenous adenosine administration significantly increased human brown adipose tissue perfusion to 28.6 ml/100 g/min compared to 8.3 ml/100 g/min at baseline.
Why the study?
Does intravenous adenosine increase brown adipose tissue perfusion and alter A2A receptor density in healthy men?
Does intravenous adenosine increase brown adipose tissue perfusion and alter A2A receptor density in healthy men?
Intravenous adenosine is a potent stimulator of human brown adipose tissue perfusion, and A2A receptors are occupied by endogenous adenosine during cold exposure, suggesting a potential target for enhancing BAT metabolism.
Answers are grounded in this paper and cite their sources.
Adenosine may probe BAT perfusion in research settings; leaves open A2A targeting to enhance metabolism in patients.
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. 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. 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. 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.
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Lahesmaa et al. (2018) studied Healthy volunteers (n=10). Intravenous adenosine vs. Baseline (room temperature) was evaluated on Brown adipose tissue (BAT) perfusion (ml/100 g/min) (p=<0.01). Intravenous adenosine administration significantly increased human brown adipose tissue perfusion to 28.6 ml/100 g/min compared to 8.3 ml/100 g/min at baseline.
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