Feeding behaviour is influenced by two primary factors: homoeostatic needs driven by hunger and hedonic desires for pleasure even in the absence of hunger. While efficient homoeostatic feeding is vital for survival, excessive hedonic feeding can lead to adverse consequences such as obesity and metabolic dysregulations. However, the neurobiological mechanisms that orchestrate homoeostatic versus hedonic food consumption remain largely unknown. Here we show that GABAergic proenkephalin (Penk) neurons in the diagonal band of Broca (DBB) of male mice respond to food presentation. We further demonstrate that a subset of DBB^Penk neurons that project to the paraventricular nucleus of the hypothalamus are preferentially activated upon food presentation during fasting periods and transmit a positive valence to facilitate feeding. On the other hand, a separate subset of DBB^Penk neurons that project to the lateral hypothalamus are preferentially activated when detecting a high-fat high-sugar (HFHS) diet and transmit a negative valence to inhibit food consumption. Notably, when given free choice of chow and HFHS diets, mice with the whole DBB^Penk population ablated exhibit reduced consumption of chow but increased intake of the HFHS diet, resulting in accelerated development of obesity and metabolic disturbances. Together, we identify a molecularly defined neural population in male mice that is crucial for the maintenance of energy balance by facilitating homoeostatic feeding while suppressing hedonic overeating.

进食行为受到两个主要因素的影响：饥饿驱动的稳态需求和即使在没有饥饿的情况下对快乐的享乐欲望。虽然有效的稳态喂养对于生存至关重要，但过度的享乐喂养可能会导致肥胖和代谢失调等不良后果。然而，协调稳态与享乐食物消耗的神经生物学机制仍然很大程度上未知。在这里，我们展示了雄性小鼠布罗卡（DBB）对角带中的 GABA 能脑啡肽原（Penk）神经元对食物呈现的反应。我们进一步证明，投射到下丘脑室旁核的 DBB ^Penk神经元子集在禁食期间出现食物时优先被激活，并传递正价以促进进食。另一方面，当检测到高脂肪高糖（HFHS）饮食时，投射到下丘脑外侧的 DBB ^Penk神经元的一个单独子集会优先被激活，并传递负价以抑制食物消耗。值得注意的是，当自由选择食物和 HFHS 饮食时，整个 DBB ^Penk群体被消除的小鼠表现出食物消耗量减少，但 HFHS 饮食摄入量增加，导致肥胖和代谢紊乱的加速发展。我们共同确定了雄性小鼠中分子定义的神经群，该神经群通过促进稳态喂养同时抑制享乐性暴饮暴食，对于维持能量平衡至关重要。