GLP-1 increases preingestive satiation via hypothalamic circuits in mice and humans.
Science
; 385(6707): 438-446, 2024 Jul 26.
Article
in En
| MEDLINE
| ID: mdl-38935778
ABSTRACT
Glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs) are effective antiobesity drugs. However, the precise central mechanisms of GLP-1RAs remain elusive. We administered GLP-1RAs to patients with obesity and observed a heightened sense of preingestive satiation. Analysis of human and mouse brain samples pinpointed GLP-1 receptor (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 that an intricate interplay between DMHGLP-1R neurons and neuropeptide Y/agouti-related peptide neurons of the arcuate nucleus (ARCNPY/AgRP neurons) occurs to regulate food intake. Our findings reveal a hypothalamic mechanism through which GLP-1RAs control preingestive satiation, offering previously unexplored neural targets for obesity and metabolic diseases.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Satiation
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Arcuate Nucleus of Hypothalamus
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Dorsomedial Hypothalamic Nucleus
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Glucagon-Like Peptide-1 Receptor Agonists
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Obesity
Limits:
Animals
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Female
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Humans
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Male
Language:
En
Journal:
Science
Year:
2024
Document type:
Article