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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1 August 2022
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July 07 2022
Delineating a serotonin 1B receptor circuit for appetite suppression in mice
Li Li
,
Li Li
(Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Validation, Visualization, Writing - original draft, Writing - review & editing)
1
The Hypothalamic Research Center, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX
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Steven C. Wyler
,
Steven C. Wyler
(Investigation)
1
The Hypothalamic Research Center, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX
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Luis A. León-Mercado
,
Luis A. León-Mercado
(Investigation, Resources)
1
The Hypothalamic Research Center, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX
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Baijie Xu
,
Baijie Xu
(Investigation, Writing - review & editing)
1
The Hypothalamic Research Center, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX
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Youjin Oh
,
Youjin Oh
(Resources, Validation)
4
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Korea
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Swati
,
Swati
(Investigation, Validation)
1
The Hypothalamic Research Center, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX
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Xiameng Chen
,
Xiameng Chen
(Data curation)
1
The Hypothalamic Research Center, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX
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Rong Wan
,
Rong Wan
(Data curation)
1
The Hypothalamic Research Center, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX
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Amanda G. Arnold
,
Amanda G. Arnold
(Investigation)
1
The Hypothalamic Research Center, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX
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Lin Jia
,
Lin Jia
(Data curation)
5
Department of Biological Sciences, The University of Texas at Dallas, Richardson, TX
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Guanlin Wang
,
Guanlin Wang
(Formal analysis, Software)
6
Centre for Computational Biology, Medical Research Council Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK
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Katherine Nautiyal
,
Katherine Nautiyal
(Methodology, Resources, Writing - review & editing)
7
Department of Psychological and Brain Sciences, Dartmouth College, Hanover, NH
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René Hen
,
René Hen
(Conceptualization, Writing - review & editing)
8
Department of Psychiatry, Columbia University and Research Foundation for Mental Hygiene, New York State Psychiatric Institute, New York, NY
9
Department of Neuroscience, Columbia University, New York, NY
10
Department of Pharmacology, Columbia University, New York, NY
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Jong-Woo Sohn
,
(Formal analysis, Funding acquisition, Investigation, Project administration, Writing - original draft, Writing - review & editing)
4
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Korea
Jong-Woo Sohn: jwsohn@kaist.ac.kr
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Chen Liu
(Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Supervision, Validation, Visualization, Writing - original draft, Writing - review & editing)
1
The Hypothalamic Research Center, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX
2
Department of Neuroscience, UT Southwestern Medical Center, Dallas, TX
3
Peter O’Donnell Jr. Brain Institute, UT Southwestern Medical Center, Dallas, TX
Correspondence to Chen Liu: chen.liu@utsouthwestern.edu
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Li Li
Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Validation, Visualization, Writing - original draft, Writing - review & editing
1
The Hypothalamic Research Center, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX
Steven C. Wyler
Investigation
1
The Hypothalamic Research Center, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX
Luis A. León-Mercado
Investigation, Resources
1
The Hypothalamic Research Center, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX
Baijie Xu
Investigation, Writing - review & editing
1
The Hypothalamic Research Center, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX
Youjin Oh
Resources, Validation
4
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Korea
Swati
Investigation, Validation
1
The Hypothalamic Research Center, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX
Xiameng Chen
Data curation
1
The Hypothalamic Research Center, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX
Rong Wan
Data curation
1
The Hypothalamic Research Center, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX
Amanda G. Arnold
Investigation
1
The Hypothalamic Research Center, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX
Lin Jia
Data curation
5
Department of Biological Sciences, The University of Texas at Dallas, Richardson, TX
Guanlin Wang
Formal analysis, Software
6
Centre for Computational Biology, Medical Research Council Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK
Katherine Nautiyal
Methodology, Resources, Writing - review & editing
7
Department of Psychological and Brain Sciences, Dartmouth College, Hanover, NH
René Hen
Conceptualization, Writing - review & editing
8
Department of Psychiatry, Columbia University and Research Foundation for Mental Hygiene, New York State Psychiatric Institute, New York, NY
9
Department of Neuroscience, Columbia University, New York, NY
10
Department of Pharmacology, Columbia University, New York, NY
Jong-Woo Sohn
Formal analysis, Funding acquisition, Investigation, Project administration, Writing - original draft, Writing - review & editing
4
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon, Korea
Chen Liu
Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Supervision, Validation, Visualization, Writing - original draft, Writing - review & editing
1
The Hypothalamic Research Center, Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX
2
Department of Neuroscience, UT Southwestern Medical Center, Dallas, TX
3
Peter O’Donnell Jr. Brain Institute, UT Southwestern Medical Center, Dallas, TX
Correspondence to Chen Liu: chen.liu@utsouthwestern.edu
Jong-Woo Sohn: jwsohn@kaist.ac.kr
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.
Received:
January 03 2022
Revision Received:
April 04 2022
Accepted:
June 13 2022
Online Issn: 1540-9538
Print Issn: 0022-1007
Funding
Funder(s):
National Institutes of Health
- Award Id(s): R01 DK114036,DK130892,F32DK116427,K01AA024809
Funder(s):
National Research Foundation of Korea
- Award Id(s): 2019R1A2C2005161,2022R1A2C3005613
Funder(s):
American Heart Association
- Award Id(s): 16SDG27260001
Funder(s):
University of Texas Southwestern Medical Center
© 2022 Li et al.
2022
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
J Exp Med (2022) 219 (8): e20212307.
Article history
Received:
January 03 2022
Revision Received:
April 04 2022
Accepted:
June 13 2022
Citation
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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