SUMMARY: Emerging research shows that GLP-1 receptor agonists increase pre-meal satiety by activating neurons in the dorsomedial hypothalamus, a mechanism that may help prevent overeating and provide insight into the treatment of obesity.
This study highlights how GLP-1 influences food perception and hypothalamic responses to food cues, enhancing satiety prior to food ingestion.
Key Facts:
GLP-1 receptor agonists activate neurons in the dorsomedial hypothalamus to promote satiety. This study, conducted in obese subjects, demonstrated an increase in satiety index with GLP-1RA treatment. Optogenetic manipulation confirmed the role of hypothalamic neurons in encoding satiety prior to ingestion.
Source: AAAS
A new study shows that GLP-1 receptor agonists promote pre-meal satiety via neurons in the dorsomedial hypothalamus.
These findings provide new insight into the neural pathways by which GLP-1 receptor agonists increase satiety and prevent excessive food intake, which may play an important role in alleviating obesity.
Glucagon-like peptide-1 (GLP-1) plays a key role in signaling postprandial satiety, a phenomenon that occurs before the actual ingestion of food and allows animals to regulate their internal state and prepare for the change.
These findings suggest that GLP-1RAs may play a role in pre-ingestive satiety to control food intake. Credit: Neuroscience News
Recently, GLP-1 receptor agonists (GLP-1RAs) have proven effective in treating obesity by influencing food cognition, attenuating hypothalamic responses to food stimuli, and altering food palatability perception.
These findings suggest that GLP-1RA may play a role in pre-meal satiety and control food intake. However, the core mechanisms underlying these effects are not well understood, and the targets of GLP-1RA remain controversial.
Here, Kyu Sik Kim and colleagues present the results of a phased clinical trial in obese people.
Kim et al. conducted satiety surveys at baseline, pre-ingestion, and ingestion phases with and without GLP-1RA administration.
Results showed that GLP-1RA treatment consistently increased satiety index (overall feeling of fullness) across all phases, whereas the control group showed a decrease from baseline to the pre-ingestion phase.
During the preingestion phase, GLP-1RAs significantly increased satiety indices compared with baseline and enhanced satiety indices of future food intake, food reward, and motivation.
Through analysis of human and mouse brain samples, Kim and his colleagues identified neural circuits in the dorsomedial hypothalamus that interact with these agonists to cause appetite suppression.
Optogenetic manipulation of these neurons induced satiety, and calcium imaging demonstrated the active involvement of these neurons in encoding satiety prior to ingestion.
About this news item on neuropharmacology and hunger research
Author: Science Press Packaging Team
Source: AAAS
Contact: Science Press Packaging Team – AAAS
Image: This image is provided by Neuroscience News
Original research: Closed access.
“GLP-1 enhances preingestive satiety via hypothalamic circuits in mice and humans,” Kevin W. Williams et al., Science
Abstract
GLP-1 enhances pre-ingestive satiety via hypothalamic circuits in mice and humans
GLP-1 receptor agonists (GLP-1RA) are effective anti-obesity drugs. However, the exact central mechanism of GLP-1RA remains unclear. We administered GLP-1RA to obese patients and observed an increase in pre-ingestive satiety.
Analysis of human and mouse brain samples identified GLP-1R neurons in the dorsomedial hypothalamus (DMH) as candidates encoding preingestive satiety, and optogenetic manipulation of DMHGLP-1R neurons induced satiety.
Calcium imaging demonstrated that these neurons are actively involved in encoding pre-feeding satiety. GLP-1RA administration selectively increased the activity of DMHGLP-1R neurons during feeding behavior. Furthermore, we identified a complex interplay between DMHGLP-1R neurons and arcuate NPY/AgRP neurons (ARCNPY/AgRP) that regulates food intake.
Our findings reveal a hypothalamic mechanism by which GLP-1RAs regulate preingestive satiety and point to a new neural target for obesity and metabolic disease.
