Summary: A new study shows GLP-1 receptor agonists increase pre-meal fullness by activating neurons in the dorsomedial hypothalamus. This mechanism helps prevent overeating, offering insights into obesity treatment.
The research highlights how GLP-1 impacts food perception and hypothalamic responses to food cues, enhancing satiation before food intake.
Key Facts:
- GLP-1 receptor agonists activate neurons in the dorsomedial hypothalamus to promote fullness.
- The study involved clinical trials with obese individuals, showing increased satiation indices with GLP-1RA treatment.
- Optogenetic manipulation confirmed the role of hypothalamic neurons in encoding preingestive satiation.
Source: AAAS
GLP-1 receptor agonists promote the feeling of fullness before eating via neurons in the dorsomedial hypothalamus, according to a new study.
The findings offer new insights into the neural pathways by which GLP-1 receptor agonists increase the feeling of fullness to prevent overconsumption of food, which is key in mitigating obesity.
Glucagon-like-peptide-1 (GLP-1) plays an important role in signaling the feeling of fullness after eating. Preingestive satiation is a phenomenon that occurs before actual food intake, allowing animals to regulate internal status and prepare for changes.
Recently, GLP-1 receptor agonists (GLP-1RAs) have proven effective in treating obesity by affecting food cognition, diminishing hypothalamic responses to food cues, and altering food palatability perception.
These findings suggest that GLP-1RAs may play a role in preingestive satiation to control food intake. However, the central mechanisms underlying these effects are poorly understood, and the targets of GLP-1RAs remain controversial.
Here, Kyu Sik Kim and colleagues present the results of a phase-specific clinical trial involving obese individuals.
Kim et al. conducted satiation surveys at baseline, pre-ingestive, and ingestive phases, with or without GLP-1RA treatment.
The results showed that GLP-1RA treatment consistently increased the satiation index (overall feeling of fullness) across all phases, while the control group showed a decline from baseline to pre-ingestive phase.
In the pre-ingestive phase, GLP-1RA significantly increased the satiation index compared to baseline, enhancing prospective food ingestion, food reward, and motivation satiation indices.
Through analysis of human and mouse brain samples, Kim et al. identified neural circuits in the dorsomedial hypothalamus that interact with these agonists to induce dampening of the desire for food.
Optogenetic manipulation of these neurons caused satiation and calcium imaging demonstrated their active involvement in encoding preingestive satiation.
About this neuropharmacology and hunger research news
Author: Science Press Package Team
Source: AAAS
Contact: Science Press Package Team – AAAS
Image: The image is credited to Neuroscience News
Original Research: Closed access.
“GLP-1 increases pre-ingestive satiation via hypothalamic circuits in mice and humans” by Kevin W. Williams et al. Science
Abstract
GLP-1 increases pre-ingestive satiation via hypothalamic circuits in mice and humans
GLP-1 receptor agonists (GLP-1RAs) are effective anti-obesity drugs. However, the precise central mechanisms of GLP-1RAs remain elusive. We administered GLP-1RAs to obese patients and observed heightened sense of preingestive satiation.
Analysis of human and mouse brain samples pinpointed GLP-1R neurons in the dorsomedial hypothalamus (DMH) as candidates for encoding preingestive satiation. Optogenetic manipulation of DMHGLP-1R neurons caused satiation.
Calcium imaging demonstrated that these neurons are actively involved in encoding preingestive satiation. GLP-1RA administration increased the activity of DMHGLP-1R neurons selectively during eating behavior. We further identified an intricate interplay between DMHGLP-1R neurons and arcuate NPY/AgRP neurons (ARCNPY/AgRP), to regulate food intake.
Our findings reveal a hypothalamic mechanism through which GLP-1RAs control preingestive satiation, offering novel neural targets for obesity and metabolic diseases.
Sarah Carter is a health and wellness expert residing in the UK. With a background in healthcare, she offers evidence-based advice on fitness, nutrition, and mental well-being, promoting healthier living for readers.
