Schulz Corinna, Vezzani Cecilia, Kroemer Nils B
Department of Psychiatry and Psychotherapy, Tübingen Center for Mental Health, University of Tübingen, Tübingen, Germany.
Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany.
Physiol Behav. 2023 May 1;263:114111. doi: 10.1016/j.physbeh.2023.114111. Epub 2023 Feb 3.
The gastrointestinal hormones ghrelin and glucagon-like peptide-1 (GLP-1) have opposite secretion patterns, as well as opposite effects on metabolism and food intake. Beyond their role in energy homeostasis, gastrointestinal hormones have also been suggested to modulate the reward system. However, the potential of ghrelin and GLP-1 to modulate reward responses in humans has not been systematically reviewed before. To evaluate the convergence of published results, we first conduct a multi-level kernel density meta-analysis of studies reporting a positive association of ghrelin (N = 353, 18 contrasts) and a negative association of GLP-1 (N = 258, 12 contrasts) and reward responses measured using task functional magnetic resonance imaging (fMRI). Second, we complement the meta-analysis using a systematic literature review, focusing on distinct reward phases and applications in clinical populations that may account for variability across studies. In line with preclinical research, we find that ghrelin increases reward responses across studies in key nodes of the motivational circuit, such as the nucleus accumbens, pallidum, putamen, substantia nigra, ventral tegmental area, and the dorsal mid insula. In contrast, for GLP-1, we did not find sufficient convergence in support of reduced reward responses. Instead, our systematic review identifies potential differences of GLP-1 on anticipatory versus consummatory reward responses. Based on a systematic synthesis of available findings, we conclude that there is considerable support for the neuromodulatory potential of gut-based circulating peptides on reward responses. To unlock their potential for clinical applications, it may be useful for future studies to move beyond anticipated rewards to cover other reward facets.
胃肠道激素胃饥饿素和胰高血糖素样肽-1（GLP-1）具有相反的分泌模式，对新陈代谢和食物摄入也有相反的作用。除了在能量平衡中的作用外，胃肠道激素还被认为可以调节奖赏系统。然而，胃饥饿素和GLP-1调节人类奖赏反应的潜力此前尚未得到系统综述。为了评估已发表结果的一致性，我们首先对报告胃饥饿素呈正相关（N = 353，18个对比）和GLP-1呈负相关（N = 258，12个对比）以及使用任务功能磁共振成像（fMRI）测量的奖赏反应的研究进行多层次核密度荟萃分析。其次，我们通过系统的文献综述对荟萃分析进行补充，重点关注可能导致各研究结果存在差异的不同奖赏阶段以及在临床人群中的应用。与临床前研究一致，我们发现胃饥饿素在多项研究中增加了动机回路关键节点（如伏隔核、苍白球、壳核、黑质、腹侧被盖区和背侧岛叶中部）的奖赏反应。相比之下，对于GLP-1，我们没有发现足够的一致性结果来支持其降低奖赏反应。相反，我们的系统综述确定了GLP-1在预期奖赏反应与 consummatory 奖赏反应方面的潜在差异。基于对现有研究结果的系统综合，我们得出结论，有相当多的证据支持肠道循环肽对奖赏反应的神经调节潜力。为了挖掘它们在临床应用中的潜力，未来的研究可能有必要超越预期奖赏，涵盖其他奖赏方面。
