Gαi/o-coupled Htr2c in the paraventricular nucleus of the hypothalamus antagonizes the anorectic effect of serotonin agents

Summary: The anorexigenic effect of serotonergic compounds has largely been attributed to activation of serotonin 2C receptors (Htr2cs). Using mouse genetic models in which Htr2c can be selectively deleted or restored (in Htr2c-null mice), we investigate the role of Htr2c in forebrain Sim1 neurons....

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Autores principales:	Eun-Seon Yoo, Li Li, Lin Jia, Caleb C. Lord, Charlotte E. Lee, Shari G. Birnbaum, Claudia R. Vianna, Eric D. Berglund, Kathryn A. Cunningham, Yong Xu, Jong-Woo Sohn, Chen Liu
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Htr2c feeding obesity KATP lorcaserin hypothalamus Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/35dc83b9b582460d887dc765f85d34a0
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spelling	oai:doaj.org-article:35dc83b9b582460d887dc765f85d34a02021-11-18T04:47:50ZGαi/o-coupled Htr2c in the paraventricular nucleus of the hypothalamus antagonizes the anorectic effect of serotonin agents2211-124710.1016/j.celrep.2021.109997https://doaj.org/article/35dc83b9b582460d887dc765f85d34a02021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2211124721014765https://doaj.org/toc/2211-1247Summary: The anorexigenic effect of serotonergic compounds has largely been attributed to activation of serotonin 2C receptors (Htr2cs). Using mouse genetic models in which Htr2c can be selectively deleted or restored (in Htr2c-null mice), we investigate the role of Htr2c in forebrain Sim1 neurons. Unexpectedly, we find that Htr2c acts in these neurons to promote food intake and counteract the anorectic effect of serotonergic appetite suppressants. Furthermore, Htr2c marks a subset of Sim1 neurons in the paraventricular nucleus of the hypothalamus (PVH). Chemogenetic activation of these neurons in adult mice suppresses hunger, whereas their silencing promotes feeding. In support of an orexigenic role of PVH Htr2c, whole-cell patch-clamp experiments demonstrate that activation of Htr2c inhibits PVH neurons. Intriguingly, this inhibition is due to Gαi/o-dependent activation of ATP-sensitive K+ conductance, a mechanism of action not identified previously in the mammalian nervous system.Eun-Seon YooLi LiLin JiaCaleb C. LordCharlotte E. LeeShari G. BirnbaumClaudia R. ViannaEric D. BerglundKathryn A. CunninghamYong XuJong-Woo SohnChen LiuElsevierarticleHtr2cfeedingobesityKATPlorcaserinhypothalamusBiology (General)QH301-705.5ENCell Reports, Vol 37, Iss 7, Pp 109997- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Htr2c feeding obesity KATP lorcaserin hypothalamus Biology (General) QH301-705.5
spellingShingle	Htr2c feeding obesity KATP lorcaserin hypothalamus Biology (General) QH301-705.5 Eun-Seon Yoo Li Li Lin Jia Caleb C. Lord Charlotte E. Lee Shari G. Birnbaum Claudia R. Vianna Eric D. Berglund Kathryn A. Cunningham Yong Xu Jong-Woo Sohn Chen Liu Gαi/o-coupled Htr2c in the paraventricular nucleus of the hypothalamus antagonizes the anorectic effect of serotonin agents
description	Summary: The anorexigenic effect of serotonergic compounds has largely been attributed to activation of serotonin 2C receptors (Htr2cs). Using mouse genetic models in which Htr2c can be selectively deleted or restored (in Htr2c-null mice), we investigate the role of Htr2c in forebrain Sim1 neurons. Unexpectedly, we find that Htr2c acts in these neurons to promote food intake and counteract the anorectic effect of serotonergic appetite suppressants. Furthermore, Htr2c marks a subset of Sim1 neurons in the paraventricular nucleus of the hypothalamus (PVH). Chemogenetic activation of these neurons in adult mice suppresses hunger, whereas their silencing promotes feeding. In support of an orexigenic role of PVH Htr2c, whole-cell patch-clamp experiments demonstrate that activation of Htr2c inhibits PVH neurons. Intriguingly, this inhibition is due to Gαi/o-dependent activation of ATP-sensitive K+ conductance, a mechanism of action not identified previously in the mammalian nervous system.
format	article
author	Eun-Seon Yoo Li Li Lin Jia Caleb C. Lord Charlotte E. Lee Shari G. Birnbaum Claudia R. Vianna Eric D. Berglund Kathryn A. Cunningham Yong Xu Jong-Woo Sohn Chen Liu
author_facet	Eun-Seon Yoo Li Li Lin Jia Caleb C. Lord Charlotte E. Lee Shari G. Birnbaum Claudia R. Vianna Eric D. Berglund Kathryn A. Cunningham Yong Xu Jong-Woo Sohn Chen Liu
author_sort	Eun-Seon Yoo
title	Gαi/o-coupled Htr2c in the paraventricular nucleus of the hypothalamus antagonizes the anorectic effect of serotonin agents
title_short	Gαi/o-coupled Htr2c in the paraventricular nucleus of the hypothalamus antagonizes the anorectic effect of serotonin agents
title_full	Gαi/o-coupled Htr2c in the paraventricular nucleus of the hypothalamus antagonizes the anorectic effect of serotonin agents
title_fullStr	Gαi/o-coupled Htr2c in the paraventricular nucleus of the hypothalamus antagonizes the anorectic effect of serotonin agents
title_full_unstemmed	Gαi/o-coupled Htr2c in the paraventricular nucleus of the hypothalamus antagonizes the anorectic effect of serotonin agents
title_sort	gαi/o-coupled htr2c in the paraventricular nucleus of the hypothalamus antagonizes the anorectic effect of serotonin agents
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/35dc83b9b582460d887dc765f85d34a0
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Gαi/o-coupled Htr2c in the paraventricular nucleus of the hypothalamus antagonizes the anorectic effect of serotonin agents

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