AIM Since foods with high hedonic value are often consumed in excess of energetic needs, this study was designed to identify the mechanisms that may counter anorexigenic signalling in the presence of hedonic foods in lean animals. METHODS Mice, in different states of satiety (fed/fasted, or fed/fasted and treated with ghrelin or leptin, respectively), were allowed to choose between high-fat/high-sucrose and standard foods. Intake of each food type and the activity of hypothalamic neuropetidergic neurons that regulate appetite were monitored. In some cases, food choice was monitored in leptin-injected fasted mice that received microinjections of galanin receptor agonists into the lateral hypothalamus. RESULTS Appetite-stimulating orexin neurons in the lateral hypothalamus are rapidly activated when lean, satiated mice consume a highly palatable food (PF); such activation (upregulated c-Fos expression) occurred even after administration of the anorexigenic hormone leptin and despite intact leptin signalling in the hypothalamus. The ability of leptin to restrain PF eating is restored when a galanin receptor 2 (Gal2R) agonist is injected into the lateral hypothalamus. CONCLUSION Hedonically-loaded foods interrupt the inhibitory actions of leptin on orexin neurons and interfere with the homeostatic control of feeding. Overeating of palatable foods can be curtailed in lean animals by activating Gal2R in the lateral hypothalamus.

中文翻译：

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可通过激活下丘脑外侧的甘丙肽2受体（Gal2R）来恢复享乐暴饮暴食期间瘦弱的瘦素敏感性。

目的由于享乐价值高的食物经常被消耗超过能量需求，因此本研究旨在确定瘦肉动物中享乐食物存在时可能对抗厌食信号的机制。方法允许处于饱腹状态不同的小鼠（分别喂食/禁食，或喂食/禁食并用生长素释放肽或瘦素治疗）在高脂/高蔗糖和标准食物之间进行选择。监测每种食物的摄入量以及调节食欲的下丘脑神经彼得皮特能神经元的活性。在某些情况下，在注射了瘦素的禁食小鼠中监测了食物的选择，这些小鼠接受了甘丙肽受体激动剂向下丘脑外侧的微注射。结果倾斜时，下丘脑外侧的食欲刺激性食欲素神经元被迅速激活，饱足的老鼠会食用高度可口的食物（PF）；即使在给予厌食激素荷尔蒙瘦素后，尽管在下丘脑中仍存在完整的瘦素信号传导，仍会发生这种激活（c-Fos表达上调）。将甘丙肽受体2（Gal2R）激动剂注射到下丘脑外侧后，瘦素抑制PF进食的能力得以恢复。结论高负荷食物会破坏瘦素对食欲素神经元的抑制作用，并干扰喂养的稳态控制。通过激活下丘脑外侧的Gal2R，可以减少瘦肉动物的暴饮暴食。将甘丙肽受体2（Gal2R）激动剂注射到下丘脑外侧后，瘦素抑制PF进食的能力得以恢复。结论高负荷食物会破坏瘦素对食欲素神经元的抑制作用，并干扰喂养的体内稳态。通过激活下丘脑外侧的Gal2R，可以减少瘦肉动物的暴饮暴食。将甘丙肽受体2（Gal2R）激动剂注射到下丘脑外侧后，瘦素抑制PF进食的能力得以恢复。结论高负荷食物会破坏瘦素对食欲素神经元的抑制作用，并干扰喂养的稳态控制。通过激活下丘脑外侧的Gal2R，可以减少瘦肉动物的暴饮暴食。