Maintaining healthy body weight is increasingly difficult in our obesogenic environment. Dieting efforts are often overpowered by the internal drive to consume energy-dense foods. Although the selection of calorically rich substrates over healthier options is identifiable across species, the mechanisms behind this choice remain poorly understood. Using a passive devaluation paradigm, we found that exposure to high-fat diet (HFD) suppresses the intake of nutritionally balanced standard chow diet (SD) irrespective of age, sex, body mass accrual and functional leptin or melanocortin-4 receptor signaling. Longitudinal recordings revealed that this SD devaluation and subsequent shift toward HFD consumption is encoded at the level of hypothalamic agouti-related peptide neurons and mesolimbic dopamine signaling. Prior HFD consumption vastly diminished the capacity of SD to alleviate the negative valence associated with hunger and the rewarding properties of food discovery even after periods of HFD abstinence. These data reveal a neural basis behind the hardships of dieting.

在我们的致肥胖环境中，保持健康的体重越来越困难。节食的努力通常被消耗高能量食品的内部动力所压倒。尽管可以通过物种识别出热量丰富的底物而不是健康的选择，但这种选择背后的机制仍然知之甚少。使用被动贬值范式，我们发现暴露于高脂饮食（HFD）会抑制营养均衡的标准饮食（SD）的摄入，而与年龄，性别，应计体重和功能性瘦素或黑皮质素4受体信号无关。纵向记录显示，此SD贬值以及随后向HFD消耗的转移编码在下丘脑刺痛相关肽神经元和中脑边缘多巴胺信号传导水平。先前的HFD消费量大大降低了SD缓解与饥饿相关的负价和发现食物后的有益特性的能力，即使在HFD戒断一段时间后也是如此。这些数据揭示了节食困难背后的神经基础。