解码中枢 LEAP2 对食物摄入量的影响及其对蓄积性多巴胺释放的影响

IF 6.7 2区 医学 Q1 NEUROSCIENCES Progress in Neurobiology Pub Date : 2024-04-17 DOI:10.1016/j.pneurobio.2024.102615
Maximilian Tufvesson-Alm, Qian Zhang, Cajsa Aranäs, Sebastian Blid Sköldheden, Christian E. Edvardsson, Elisabet Jerlhag
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引用次数: 0

摘要

肠脑肽胃泌素及其受体被认为是饥饿和奖赏过程的调节剂。然而,最近发现的胃泌素受体反向激动剂--肝脏表达抗菌肽2(LEAP2)的特性却不太清楚。本研究旨在阐明LEAP2通过摄食对奖赏相关行为的中枢效应及其机制。对小鼠进行LEAP2中心给药,可有效减少小鼠的摄食量和对适口食物的摄入量。令人惊讶的是,LEAP2对摄食的影响与对适口食物的偏好相关。此外,LEAP2还减少了对高偏好食物的奖赏记忆,并减弱了与味觉食物暴露和进食相关的多巴胺累积释放。有趣的是,LEAP2在大脑中广泛表达,尤其是在与奖赏相关的脑区,如侧背被盖区(LDTg)。当允许自由接触适口食物时,这种表达会发生明显变化。因此,将 LEAP2 注入 LDTg 足以短暂减少急性味觉食物摄入量。综上所述,本研究结果表明,中枢 LEAP2 对与食物相关的多巴胺能奖赏信号传导有深远影响,并影响摄食的多个方面。本研究强调了 LEAP2 对奖赏的影响,这可能适用于肥胖症和其他与奖赏相关的精神和神经疾病。
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Decoding the influence of central LEAP2 on food intake and its effect on accumbal dopamine release

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.

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来源期刊
Progress in Neurobiology
Progress in Neurobiology 医学-神经科学
CiteScore
12.80
自引率
1.50%
发文量
107
审稿时长
33 days
期刊介绍: Progress in Neurobiology is an international journal that publishes groundbreaking original research, comprehensive review articles and opinion pieces written by leading researchers. The journal welcomes contributions from the broad field of neuroscience that apply neurophysiological, biochemical, pharmacological, molecular biological, anatomical, computational and behavioral analyses to problems of molecular, cellular, developmental, systems, and clinical neuroscience.
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