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.
Delineating a serotonin 1B receptor circuit for appetite suppression in mice
Disclosures: The authors declare no competing interests exist.
Guanlin Wang’s current address is Shanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology, Fudan University, Shanghai, China.
- Award Id(s): R01 DK114036,DK130892,F32DK116427,K01AA024809
- Award Id(s): 2019R1A2C2005161,2022R1A2C3005613
- Award Id(s): 16SDG27260001
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Li Li, Steven C. Wyler, Luis A. León-Mercado, Baijie Xu, Youjin Oh, Swati, Xiameng Chen, Rong Wan, Amanda G. Arnold, Lin Jia, Guanlin Wang, Katherine Nautiyal, René Hen, Jong-Woo Sohn, Chen Liu; Delineating a serotonin 1B receptor circuit for appetite suppression in mice. J Exp Med 1 August 2022; 219 (8): e20212307. doi: https://doi.org/10.1084/jem.20212307
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