The gut-brain peptide ghrelin and its receptor are established as a regulator of hunger and reward-processing. However, the recently recognized ghrelin receptor inverse agonist, liver-expressed antimicrobial peptide 2 (LEAP2), is less characterized. The present study aimed to elucidate LEAP2s central effect on reward-related behaviors through feeding and its mechanism. LEAP2 was administrated centrally in mice and effectively reduced feeding and intake of palatable foods. Strikingly, LEAP2s effect on feeding was correlated to the preference of the palatable food. Further, LEAP2 reduced the rewarding memory of high preference foods, and attenuated the accumbal dopamine release associated with palatable food exposure and eating. Interestingly, LEAP2 was widely expressed in the brain, and particularly in reward-related brain areas such as the laterodorsal tegmental area (LDTg). This expression was markedly altered when allowed free access to palatable foods. Accordingly, infusion of LEAP2 into LDTg was sufficient to transiently reduce acute palatable food intake. Taken together, the present results show that central LEAP2 has a profound effect on dopaminergic reward signaling associated with food and affects several aspects of feeding. The present study highlights LEAP2s effect on reward, which may have applications for obesity and other reward-related psychiatric and neurological disorders.

中文翻译：

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解码中枢LEAP2对食物摄入的影响及其对累积多巴胺释放的影响

肠脑肽饥饿素及其受体被确定为饥饿和奖励处理的调节剂。然而，最近公认的生长素释放肽受体反向激动剂、肝脏表达的抗菌肽 2 (LEAP2) 的特征却较少。本研究旨在阐明LEAP2通过进食对奖励相关行为的中心作用及其机制。 LEAP2在小鼠体内集中给药，有效减少了可口食物的喂养和摄入。引人注目的是，LEAP2 对进食的影响与对美味食物的偏好相关。此外，LEAP2 降低了对高偏好食物的奖励记忆，并减弱了与美味食物接触和进食相关的累积多巴胺释放。有趣的是，LEAP2 在大脑中广泛表达，特别是在与奖励相关的大脑区域，如后背被盖区 (LDTg)。当允许自由获取美味食物时，这种表达方式明显改变。因此，将 LEAP2 输注到 LDTg 中足以暂时减少急性可口食物摄入。综上所述，目前的结果表明，中枢 LEAP2 对与食物相关的多巴胺能奖励信号传导具有深远的影响，并影响喂养的多个方面。本研究强调了 LEAP2 对奖励的影响，这可能适用于肥胖和其他与奖励相关的精神和神经疾病。