Glucagon-Like Peptide 1 Receptors in Nucleus Accumbens Affect Food Intake

Abstract

Central glucagon-like peptide 1 receptor (GLP-1R) stimulation suppresses food intake, and hindbrain GLP-1 neurons project to numerous feeding-relevant brain regions. One such region is the nucleus accumbens (NAc), which plays a role in reward and motivated behavior. Using immunohistochemical and retrograde tracing techniques in rats, we identified a robust projection from GLP-1 neurons in the nucleus of the solitary tract to the NAc. We hypothesized that activation of NAc GLP-1Rs suppresses feeding. When injected into the NAc core of rats at doses subthreshold for effect when administered to the lateral ventricle, GLP-1 significantly reduced food intake relative to vehicle at 1, 2, and 24 h posttreatment. The same doses had no effect when injected into the NAc shell. NAc core treatment with ventricle-subthreshold doses of the GLP-1R antagonist exendin (9–39) caused significant hyperphagia at 2 h posttreatment, suggesting that endogenous stimulation of NAc core GLP-1Rs plays a role in limiting food intake. It has been suggested that GLP-1 can cause nausea, but we found that NAc core administration of GLP-1 did not cause a conditioned taste aversion to saccharin, suggesting that the anorexic effect of NAc core GLP-1 is not caused by malaise. Finally, we observed that NAc core injection of GLP-1 significantly increased c-Fos expression in the NAc core. We conclude that that GLP-1Rs in the NAc play a physiologic role in food intake control, and suggest that the GLP-1 projection to NAc core may link satiation signal processing in the hindbrain with forebrain processing of food reward.

Effects of glucagon-like peptide 1 on appetite and body weight: focus on the CNS

“…sucrose in rats (Dickson et al 2012). Also, injection of exendin 9-39 into the NAc resulted in significant hyperphagia in rats, indicating a physiologic role of GLP-1 receptors in the NAc for the control of food intake (Dossat et al 2011). Collectively, these preclinical data show that central GLP-1 induces satiety by affecting both homeostatic and reward-associated food intake and that these effects seem to be GLP-1 receptor-mediated.…”

The arcuate nucleus mediates GLP-1 receptor agonist liraglutide-dependent weight loss

“…Numerous comprehensive studies aim to describe the GLP-1R population responsible for GLP-1-induced energy intake reduction (20,(33)(34)(35)(36)(37)(38)(39)(40)(41). This task has been hampered by the widespread distribution of the GLP-1R in the brain and in the periphery on neurons that could rapidly signal to the brain.…”

Activation of murine pre-proglucagon–producing neurons reduces food intake and body weight

“…Furthermore, GLP-1 has also been shown to induce pica (18) and conditioned taste aversion (19), through action at GLP-1Rs expressed at specific neuroanatomical sites that are distinct from those regulating satiety (20)(21)(22)(23).…”