Caffeine inhibits hypothalamic A(1)R to excite oxytocin neuron and ameliorate dietary obesity in mice.
Caffeine inhibits hypothalamic A(1)R to excite oxytocin neuron and ameliorate dietary obesity in mice.
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咖啡因抑制下丘脑 A1R 兴奋催产素神经元并改善小鼠饮食肥胖
DOI：
10.1038/ncomms15904
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发表时间：
2017-06-27
影响因子：
16.6
通讯作者：
Zhang G
中科院分区：
文献类型：
--
作者：
Wu L;Meng J;Shen Q;Zhang Y;Pan S;Chen Z;Zhu LQ;Lu Y;Huang Y;Zhang G
咖啡因是腺苷受体A1 R的拮抗剂，被用作膳食补充剂以减轻体重，尽管其潜在机制尚不清楚。在这里，我们报告说，腺苷水平在脑脊液中，下丘脑A1受体的表达，增加了饮食诱导的肥胖（DIO）小鼠。我们发现，在下丘脑室旁核（PVN）神经元中A1R过表达的小鼠具有高摄食性、糖耐量和高体重。中枢或外周给予咖啡因可通过抑制食欲和增加能量消耗来降低DIO小鼠的体重。我们还表明，咖啡因兴奋催产素表达的神经元，和催产素的行动的阻断显着减弱咖啡因对能量平衡的影响。这些数据表明，咖啡因抑制PVN催产素神经元上表达的A1R负调节DIO小鼠的能量平衡。腺苷受体拮抗剂咖啡因调节代谢的机制尚不清楚。在这里，作者表明，腺苷A1R受体表达增加饮食诱导的肥胖小鼠的下丘脑，体重可以减轻咖啡因通过其对下丘脑催产素神经元的作用，通过中央管理。
Caffeine, an antagonist of the adenosine receptor A1R, is used as a dietary supplement to reduce body weight, although the underlying mechanism is unclear. Here, we report that adenosine level in the cerebrospinal fluid, and hypothalamic expression of A1R, are increased in the diet-induced obesity (DIO) mouse. We find that mice with overexpression of A1R in the neurons of paraventricular nucleus (PVN) of the hypothalamus are hyperphagic, have glucose intolerance and high body weight. Central or peripheral administration of caffeine reduces the body weight of DIO mice by the suppression of appetite and increasing of energy expenditure. We also show that caffeine excites oxytocin expressing neurons, and blockade of the action of oxytocin significantly attenuates the effect of caffeine on energy balance. These data suggest that caffeine inhibits A1Rs expressed on PVN oxytocin neurons to negatively regulate energy balance in DIO mice. The mechanism by which caffeine, an antagonist of adenosine receptors, regulates metabolism is not clear. Here the authors show that adenosine A1R receptor expression is increased in the hypothalamus of diet-induced obesity mice, and that body weight can be alleviated by central administration of caffeine via its action on hypothalamic oxytocin neurons.