Glucagon‐Like Peptide‐1 Receptor Agonist Administration Suppresses Both Water and Saline Intake in Rats

Abstract

Glucagon-like peptide-1 (GLP-1) plays an important role in energy homeostasis. Injections of GLP-1 receptor (GLP-1R) agonists suppress food intake, and endogenous GLP-1 is released when nutrients enter the gut. There is also growing evidence that the GLP-1 system is involved in the regulation of body fluid homeostasis. GLP-1R agonists suppress water intake independent of their effects on food intake. It is unknown, however, whether this suppressive effect of GLP-1R agonists extends to saline intake. Accordingly, we tested the effect of the GLP-1R agonists liraglutide (0.05 µg) and exendin-4 (0.05 µg) on water and saline intakes stimulated either by angiotensin II (AngII) or by water deprivation with partial rehydration (WD-PR). Each agonist suppressed AngII-induced water intake; however, only exendin-4 suppressed saline intake. WD-PR-induced water and saline intakes were both attenuated by each agonist. Analysis of drinking microstructure after WD-PR found a reliable effect of the agonists on burst number. Furthermore, exendin-4 conditioned a robust taste avoidance to saccharine; however, there was no similar effect of liraglutide. To evaluate the relevance of the conditioned taste avoidance, we tested whether inducing visceral malaise by injection of lithium chloride (LiCl) suppressed fluid intake. Injection of LiCl did not suppress water or saline intakes. Overall, these results indicate that the fluid intake suppression by GLP-1R activation is not selective to water intake, is a function of post-ingestive feedback, and is not secondary to visceral malaise.

The glucagon‐like peptide 1 receptor agonist liraglutide attenuates the reinforcing properties of alcohol in rodents

“…Moreover, we used lower doses than those causing a taste aversion (Kanoski et al ), and we followed up the acute studies with repeated administration of liraglutide, a design with documented tolerance for nausea. This is further substantiated by the findings that liraglutide, in contrast to Ex4, does not condition a taste avoidance to saccharine in mice (McKay & Daniels ).…”

Glucagon-like peptide 1 (GLP-1)

“…GLP-1 inhibition of water intake was first reported by Mads Tang-Christensen in 1996 [92] and was later confirmed by others [[755], [756], [757], [758], [759], [760]]. GLP-1 inhibition of water consumption is independent of food intake [758] and is blocked by pretreatment with exendin (9–39) [92].…”

Roux-en-Y gastric bypass does not affect daily water intake or the drinking response to dipsogenic stimuli in rats

“…Although the contributions of mechanoreceptors in the gut and hormonal signaling to the brain are well known to participate in the control of food intake, much less is known about the signals that affect fluid intake satiation. Some parallels seem to exist, however, and recent studies have shown that some of the same gut hormones that affect food intake also have effects on fluid intake (21,27,28,30,31,36,42). The role of feedback from the gut in the control of fluid intake, however, remains poorly understood.…”