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Publication : Delineating a serotonin 1B receptor circuit for appetite suppression in mice.

First Author  Li L Year  2022
Journal  J Exp Med Volume  219
Issue  8 PubMed ID  35796804
Mgi Jnum  J:332532 Mgi Id  MGI:7424770
Doi  10.1084/jem.20212307 Citation  Li L, et al. (2022) Delineating a serotonin 1B receptor circuit for appetite suppression in mice. J Exp Med 219(8)
abstractText  Triptans are a class of commonly prescribed antimigraine drugs. Here, we report a previously unrecognized role for them to suppress appetite in mice. In particular, frovatriptan treatment reduces food intake and body weight in diet-induced obese mice. Moreover, the anorectic effect depends on the serotonin (5-HT) 1B receptor (Htr1b). By ablating Htr1b in four different brain regions, we demonstrate that Htr1b engages in spatiotemporally segregated neural pathways to regulate postnatal growth and food intake. Moreover, Htr1b in AgRP neurons in the arcuate nucleus of the hypothalamus (ARH) contributes to the hypophagic effects of HTR1B agonists. To further study the anorexigenic Htr1b circuit, we generated Htr1b-Cre mice. We find that ARH Htr1b neurons bidirectionally regulate food intake in vivo. Furthermore, single-nucleus RNA sequencing analyses revealed that Htr1b marks a subset of AgRP neurons. Finally, we used an intersectional approach to specifically target these neurons (Htr1bAgRP neurons). We show that they regulate food intake, in part, through a Htr1bAgRP-->PVH circuit.
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