Glucagon-Like Peptide-1 and Hypothalamic Regulation of Satiation: Cognitive and Neural Insights from Human and Animal Studies

May 14, 2025Diabetes & metabolism journal

How Glucagon-Like Peptide-1 Helps the Brain Control Fullness: Cognitive and Brain Findings from Humans and Animals

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Abstract

GLP-1 receptor agonists influence brain activity during food cognition, potentially enhancing pre-ingestive .

GLP-1 plays a key role in regulating blood sugar levels by increasing insulin secretion and inhibiting glucagon release.
Neuroimaging studies in humans indicate that GLP-1 receptor agonists may affect brain functions related to food perception.
Animal studies suggest that the hypothalamus is involved in hunger regulation and may influence feelings of fullness.
The dorsomedial hypothalamus may mediate cognitive factors related to pre-ingestive satiation.
GLP-1 receptor neurons in the hypothalamus may regulate various feeding behaviors, highlighting potential targets for obesity treatment.

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Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as blockbuster drugs for treating metabolic diseases. Glucagon-like peptide-1 (GLP-1) plays a pivotal role in glucose homeostasis by enhancing insulin secretion, suppressing glucagon release, delaying gastric emptying, and acting on the central nervous system to regulate and . This review summarizes the discovery of GLP-1 and the development of GLP-1RAs, with a particular focus on their central mechanisms of action. Human neuroimaging studies demonstrate that GLP-1RAs influence brain activity during food cognition, supporting a role in pre-ingestive satiation. Animal studies on hypothalamic feed-forward regulation of hunger suggest that cognitive hypothalamic mechanisms may also contribute to satiation control. We highlight the brain mechanisms of GLP-1RA-induced satiation and satiety, including cognitive impacts, with an emphasis on animal studies of hypothalamic glucagon-like peptide-1 receptor (GLP-1R) and GLP-1R-expressing neurons. Actions in non-hypothalamic regions are also discussed. Additionally, we review emerging combination drugs and oral GLP-1RA formulations aimed at improving efficacy and patient adherence. In conclusion, the dorsomedial hypothalamus (DMH)-a key GLP-1RA target-mediates pre-ingestive cognitive satiation, while other hypothalamic GLP-1R neurons regulate diverse aspects of feeding behavior, offering potential therapeutic targets for obesity treatment.

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Glucagon-Like Peptide-1 and Hypothalamic Regulation of Satiation: Cognitive and Neural Insights from Human and Animal Studies

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