Endogenous Hindbrain Glucagon-Like Peptide-1 Receptor Activation Contributes to the Control of Food Intake by Mediating Gastric Satiation Signaling

Mar 7, 2009Endocrinology

Natural activation of a hindbrain receptor helps control eating by signaling stomach fullness

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Abstract

Endogenous activation of central GLP-1 receptors is associated with reduced food intake after gastric distension.

Blocking GLP-1 receptors increased food intake in overnight food-deprived rats after they ingested a nutrient solution.
Direct injection of a GLP-1 receptor antagonist into the medial NTS also led to increased food intake, indicating the importance of this receptor population.
Gastric distension significantly reduced food intake, and this effect was diminished when GLP-1 receptors were blocked.
In contrast, nutrient infusion into the intestine did not change the intake suppression caused by GLP-1 receptor blockade.
These findings suggest that gastric signals play a critical role in activating GLP-1 receptors to regulate feeding behavior.

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Exogenous activation of central nervous system glucagon-like peptide-1 (GLP-1) receptors (GLP-1Rs) reduces food intake. Experiments addressed whether endogenous central GLP-1R activity is involved in the control of normal feeding and examined which gastrointestinal satiation signals contribute to this control. Given that nucleus tractus solitarius (NTS) neurons are the source of central GLP-1, that caudal brainstem circuits mediate the intake suppression triggered by exogenous hindbrain GLP-1R activation, and that these neurons process gastrointestinal vagal signals, the role of endogenous hindbrain GLP-1R activation to intake control was the focus of the analysis. Food intake increased with GLP-1R antagonist [Exendin-(9-39) (Ex-9)] [10 microg, fourth intracerebroventricular (icv)] delivery to overnight food-deprived rats after ingestion of 9 ml Ensure diet. Direct medial NTS injection of a ventricle subthreshold dose (1.0 microg) of Ex-9 increased food intake and established the contribution of this GLP-1R population to the effect observed with ventricular administration. To determine whether satiation signals of gastric vs. intestinal origin drive the GLP-1R-mediated NTS effect on food intake, two experiments were performed in overnight-fasted rats. In one, Ensure was infused intraduodenally (0.4 ml/min for 20 min); in another, the stomach was distended (9 ml SILASTIC brand balloon) for 15 min before fourth icv Ex-9. The intake suppression by duodenal nutrient infusion was not affected by GLP-1R blockade, but the feeding suppression after gastric distension was significantly attenuated by fourth icv Ex-9. We conclude that endogenous NTS GLP-1R activation driven by gastric satiation signals contributes to the control of normal feeding.

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Endogenous Hindbrain Glucagon-Like Peptide-1 Receptor Activation Contributes to the Control of Food Intake by Mediating Gastric Satiation Signaling

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