2024
DOI: 10.1126/science.adj2537
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GLP-1 increases preingestive satiation via hypothalamic circuits in mice and humans

Kyu Sik Kim,
Joon Seok Park,
Eunsang Hwang
et al.

Abstract: 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 DMH GLP-1R neurons caused satiation. Calcium imaging demonstrated tha… Show more

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Cited by 17 publications
(3 citation statements)
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“…This raises the possibility that the Glp1r DMH neurons and Trh Arc neurons convey different information to AgRP neurons. For instance, while the Glp1r DMH neurons relay pre-ingestive sensory cues to AgRP neurons 28 , the Trh Arc neurons may instead transmit postabsorptive metabolic cues, such as leptin 84 , consistent with our observation that their synaptic input largely comes from the Arc and DMH (Fig. 7L).…”
Section: Discussionsupporting
confidence: 82%
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“…This raises the possibility that the Glp1r DMH neurons and Trh Arc neurons convey different information to AgRP neurons. For instance, while the Glp1r DMH neurons relay pre-ingestive sensory cues to AgRP neurons 28 , the Trh Arc neurons may instead transmit postabsorptive metabolic cues, such as leptin 84 , consistent with our observation that their synaptic input largely comes from the Arc and DMH (Fig. 7L).…”
Section: Discussionsupporting
confidence: 82%
“…We assigned a neuronal subtype identity to each Arc rabies+ cells by transferring cell-type labels from a reference dataset of molecular neuron subtypes in the Arc-ME 28 (Fig. 3A,B).…”
Section: Label Transfer Predicts Molecular Subtypes Of Rabies-infecte...mentioning
confidence: 99%
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