The role of glucagon-like peptide-1 (GLP-1) in fluid and food intakes in vasopressin-deficient Brattleboro rats
The role of glucagon-like peptide-1 (GLP-1) in fluid and food intakes in vasopressin-deficient Brattleboro rats
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DOI：
10.1016/j.physbeh.2023.114093
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发表时间：
2023-01-28
影响因子：
2.9
通讯作者：
Daniels，Derek
中科院分区：
文献类型：
--
作者：
Brakey，Destiny J.;Schatz，Kelcie C.;Daniels，Derek
进食和饮水同时发生，许多控制一种的相同机制也参与控制另一种，因此很难分离出控制液体摄入的特定机制。胰高血糖素样肽-1（GLP-1）是一种似乎参与两种摄食行为的内源性控制的肽，但我们缺乏对GLP-1如何以及在何处控制液体摄入的透彻理解。加压素缺乏的Brattleboro大鼠是遗传性下丘脑性尿崩症的模型，已被广泛用于加压素在行为和生理方面的作用的研究。在这里，我们建议，这些大鼠，正常饮食，但过度饮酒，提供了一个有用的模型，分离食物和液体摄入的中枢控制。作为为这些目的建立该模型的第一步，我们专注于GLP-1。与用GLP-1受体（GLP-1 R）激动剂处理后观察到的效果类似，野生型和Brattleboro大鼠之间的摄入差异在很大程度上是舔爆发次数的函数，表明摄食后反馈的差异（例如，饱食）。当给予GLP-1 R激动剂中枢注射时，野生型和Brattleboro大鼠之间对摄食的影响相当，但Brattleboro大鼠中药物对液体摄入的影响明显夸大。此外，Brattleboro大鼠对GLP-1 R拮抗作用无反应，而野生型大鼠则有反应。综上所述，这些结果表明，Brattleboro大鼠表现出选择性破坏GLP-1的控制水的摄入。总体而言，这些实验提供了Brattleboro大鼠摄食行为的基础研究，并证明了使用这些大鼠解开GLP-1对食物和液体摄入影响的潜力。
Eating and drinking co-occur and many of the same mechanisms that control one are involved in the control of the other, making it difficult to isolate specific mechanisms for the control of fluid intake. Glucagon-like peptide-1 (GLP-1) is a peptide that seems to be involved in the endogenous control of both ingestive behaviors, but we lack a thorough understanding of how and where GLP-1 is acting to control fluid intake. Vasopressin-deficient Brattleboro rats are a model of hereditary hypothalamic diabetes insipidus that have been used extensively for the study of vasopressin actions in behavior and physiology. Here, we propose that these rats, that eat normally but drink excessively, provide a useful model to dissociate central controls of food and fluid intakes. As an initial step toward establishing this model for these purposes, we focused on GLP-1. Similar to the effect observed after treatment with a GLP-1 receptor (GLP-1R) agonist, the intake difference between wildtype and Brattleboro rats was largely a function in the number of licking bursts, indicating differences in post-ingestive feedback (e.g., satiation). When given central injections of a GLP-1R agonist, the effect on feeding was comparable between wildtype and Brattleboro rats, but the effect of drug on fluid intake was markedly exaggerated in Brattleboro rats. Additionally, Brattleboro rats did not respond to GLP-1R antagonism, whereas wildtype rats did. Taken together, these results suggest that Brattleboro rats exhibit a selective disruption to GLP-1′s control of water intake. Overall, these experiments provide foundational studies of the ingestive behavior of Brattleboro rats and demonstrate the potential to use these rats to disentangle the effects of GLP-1 on food and fluid intakes.