Knakker Balázs, Inkeller Judit, Kovács Péter, Lendvai Balázs, Hernádi István
Grastyán E. Translational Research Centre, University of Pécs, Pécs, Hungary.
Department of Pharmacology and Drug Safety Research, Gedeon Richter Plc., Budapest, Hungary.
Neuropsychopharmacology. 2024 Dec;50(2):410-418. doi: 10.1038/s41386-024-01981-5. Epub 2024 Sep 4.
Glucagon-like peptide 1 (GLP-1), a neuroendocrine signal of energy balance and satiety, has a major role in regulating food intake behaviour. Here we investigated the effects of the GLP-1 agonist exenatide on palatability-driven feeding regulation in adult male rhesus macaques (n = 5) using a novel operant food intake paradigm with four meal schedule conditions where two types of pellets with different palatability values were offered as meal in all combinations in two consecutive daily feeding sessions (S1 and S2). In control conditions, a strong, palatability-driven anticipatory effect was found in S1, followed by a complementary positive contrast effect in S2. After acute subcutaneous treatment with 1 µg/kg dose of exenatide 1 h before S1, food intake decreased to the same very low level in all meal schedule conditions in S1, completely erasing the previously observed anticipatory effect. Conversely, exenatide induced hypoglycaemia in an anticipatory meal schedule dependent pattern. Interestingly, the previously observed positive contrast effect was spared in S2, with a weaker residual effect specifically on the consumption of the more palatable pellet type. To conclude, the food intake reducing effects of exenatide may temporally evolve from strong anorectic to weak anhedonic modulations, where hedonic experience and anticipation during the early anorectic phase is conserved but uncoupled from food intake behaviour.
胰高血糖素样肽1(GLP-1)是能量平衡和饱腹感的一种神经内分泌信号,在调节食物摄入行为中起主要作用。在此,我们使用一种新颖的操作性食物摄入范式,对成年雄性恒河猴(n = 5)进行了研究,该范式有四种进餐时间表条件,在连续两天的每日喂食时段(S1和S2)中,以所有组合形式提供两种具有不同适口性值的颗粒作为餐食,以此来探究GLP-1激动剂艾塞那肽对适口性驱动的进食调节的影响。在对照条件下,在S1中发现了强烈的、由适口性驱动的预期效应,随后在S2中出现了互补的正性对比效应。在S1前1小时用1μg/kg剂量的艾塞那肽进行急性皮下治疗后,在S1的所有进餐时间表条件下,食物摄入量均降至相同的极低水平,完全消除了先前观察到的预期效应。相反,艾塞那肽以预期进餐时间表依赖的模式诱发低血糖。有趣的是,先前观察到的正性对比效应在S2中得以保留,对更可口的颗粒类型的消耗有较弱的残留效应。总之,艾塞那肽的食物摄入减少作用可能会随时间从强烈的厌食调节演变为微弱的快感缺失调节,其中在早期厌食阶段的快感体验和预期得以保留,但与食物摄入行为脱钩。