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Scientists studying obesity have had great interest in brown fat, adipose tissue that actually helps burn fat (for example, to generate body heat in the cold). Studies suggest that higher levels of brown fat correlate with lowered risks for obesity and diabetes, and scientists are studying whether activating brown fat might help in the fight against obesity. Nature recently published a paper showing that the signaling molecule adenosine activates the energy-burning function of brown fat by binding to A2A receptors on the brown fat cells. Here's the abstract for the paper:
These results are important because they suggest that drugs targeting the A2A receptor (or some of the downstream signalling pathways) could help fight obesity. Indeed, obese mice treated with drugs that activate the A2A receptor showed weight loss and improved glucose toleance.
The study, however, has potentially troubling implications. Caffeine is an A2A antagonist, meaning that it prevents activation of the A2A receptor. The results of the paper would then suggest that caffeine should inhibit energy metabolism by brown fat, negating its beneficial effects. Although the paper shows that A2A antagonist do indeed block energy expenditure by brown fat, it does not look at caffeine specifically. Given the widespread consumption of caffeine, this seems like an issue warranting further study.
A quick web searched turned up this news article linking coffee consumption and obesity, but it suggests that the polyphenols in coffee are to blame, not caffeine. Does anyone else know of any studies looking at the relationship between caffeine consumption and obesity?
(Gnad et al. 2014. Adenosine activates brown adipose tissue and recruits beige adipocytes via A2A receptors. Nature. Published online 15 October 2014. http://dx.doi.org/10.1038/nature13816 [Broken]).Brown adipose tissue (BAT) is specialized in energy expenditure, making it a potential target for anti-obesity therapies. Following exposure to cold, BAT is activated by the sympathetic nervous system with concomitant release of catecholamines and activation of β-adrenergic receptors. Because BAT therapies based on cold exposure or β-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. 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 A2A receptor is the most abundant adenosine receptor in human and murine BAT. Pharmacological blockade or genetic loss of A2A receptors in mice causes a decrease in BAT-dependent thermogenesis, whereas treatment with A2A agonists significantly increases energy expenditure. Moreover, pharmacological stimulation of A2A receptors or injection of lentiviral vectors expressing the A2A receptor into white fat induces brown-like cells—so-called beige adipocytes. Importantly, mice fed a high-fat diet and treated with an A2A agonist are leaner with improved glucose tolerance. Taken together, our results demonstrate that adenosine–A2A 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.
These results are important because they suggest that drugs targeting the A2A receptor (or some of the downstream signalling pathways) could help fight obesity. Indeed, obese mice treated with drugs that activate the A2A receptor showed weight loss and improved glucose toleance.
The study, however, has potentially troubling implications. Caffeine is an A2A antagonist, meaning that it prevents activation of the A2A receptor. The results of the paper would then suggest that caffeine should inhibit energy metabolism by brown fat, negating its beneficial effects. Although the paper shows that A2A antagonist do indeed block energy expenditure by brown fat, it does not look at caffeine specifically. Given the widespread consumption of caffeine, this seems like an issue warranting further study.
A quick web searched turned up this news article linking coffee consumption and obesity, but it suggests that the polyphenols in coffee are to blame, not caffeine. Does anyone else know of any studies looking at the relationship between caffeine consumption and obesity?
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