Molecular Connectomics Reveals a Glucagon-Like Peptide 1 Sensitive Neural Circuit for Satiety.

ABSTRACT: Liraglutide and other agonists of the glucagon-like peptide 1 receptor (GLP-1RAs) are effective weight loss drugs, but how they suppress appetite remains unclear. One potential mechanism is by activating neurons which inhibit hunger-promoting Agouti-related peptide (AgRP) neurons of the arcuate hypothalamus (Arc). To identify these afferents, we developed a method combining rabies-based connectomics with single-nuclei transcriptomics. Applying this method to AgRP neurons predicted at least 21 afferent subtypes in the mouse mediobasal and paraventricular hypothalamus. Among these are Trh+ Arc neurons, inhibitory neurons which express the Glp1r gene and are activated by the GLP-1RA liraglutide. Activating Trh+ Arc neurons inhibits AgRP neurons and feeding in an AgRP neuron-dependent manner.

SUBMITTER: Webster AN 

PROVIDER: S-EPMC10635031 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature