| Autor: |
Webster AN, Becker JJ, Li C, Schwalbe DC, Kerspern D, Karolczak EO, Bundon C, Onoharigho RA, Crook M, Jalil M, Godschall EN, Dame EG, Dawer A, Belmont-Rausch DM, Pers TH, Lutas A, Habib N, Guler AD, Krashes MJ, Campbell JN |
| Jazyk: |
angličtina |
| Zdroj: |
BioRxiv : the preprint server for biology [bioRxiv] 2024 Jul 12. Date of Electronic Publication: 2024 Jul 12. |
| DOI: |
10.1101/2023.10.31.564990 |
| Abstrakt: |
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. Silencing Trh+ Arc neurons causes over-eating and weight gain and attenuates liraglutide's effect on body weight. Our results demonstrate a widely applicable method for molecular connectomics, comprehensively identify local inputs to AgRP neurons, and reveal a circuit through which GLP-1RAs suppress appetite. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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