2. Academic Validation
  3. Delineating a serotonin 1B receptor circuit for appetite suppression in mice

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

  • J Exp Med. 2022 Aug 1;219(8):e20212307. doi: 10.1084/jem.20212307.
Li Li 1,  Steven C Wyler 1,  Luis A León-Mercado 1,  Baijie Xu 1,  Youjin Oh 2,  Swati 1,  Xiameng Chen 1,  Rong Wan 1,  Amanda G Arnold 1,  Lin Jia 3,  Guanlin Wang 4,  Katherine Nautiyal 5,  René Hen 6 7 8,  Jong-Woo Sohn 2,  Chen Liu 1 9 10
Affiliations

Affiliations

  • 1 The Hypothalamic Research Center, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX.
  • 2 Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Korea.
  • 3 Department of Biological Sciences, The University of Texas at Dallas, Richardson, TX.
  • 4 Centre for Computational Biology, Medical Research Council Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.
  • 5 Department of Psychological and Brain Sciences, Dartmouth College, Hanover, NH.
  • 6 Department of Psychiatry, Columbia University and Research Foundation for Mental Hygiene, New York State Psychiatric Institute, New York, NY.
  • 7 Department of Neuroscience, Columbia University, New York, NY.
  • 8 Department of Pharmacology, Columbia University, New York, NY.
  • 9 Department of Neuroscience, UT Southwestern Medical Center, Dallas, TX.
  • 10 Peter O'Donnell Jr. Brain Institute, UT Southwestern Medical Center, Dallas, TX.
PMID: 35796804 DOI: 10.1084/jem.20212307
Abstract

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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