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.

中文翻译：

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咖啡因抑制下丘脑A1R激发催产素神经元并改善小鼠的饮食肥胖。

咖啡因是腺苷受体A ₁ R的拮抗剂，尽管其基本机理尚不清楚，但它被用作膳食补充剂以减轻体重。在这里，我们报告在饮食诱导的肥胖症（DIO）小鼠中脑脊液中的腺苷水平和A ₁ R的下丘脑表达增加。我们发现A ₁过表达的小鼠下丘脑室旁核（PVN）神经元中的R吞噬，具有葡萄糖耐受不良和高体重。咖啡因的中枢或外周给药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，咖啡因会激发表达催产素的催产素，而对催产素作用的阻断会大大减弱咖啡因对能量平衡的影响。这些数据表明咖啡因抑制DIO小鼠PVN催产素神经元上表达的A ₁ Rs，从而负面调节能量平衡。