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

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

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number109997
JournalCell Reports
Volume37
Issue number7
DOIs
StatePublished - Nov 16 2021

Keywords

  • Htr2c
  • K
  • feeding
  • hypothalamus
  • lorcaserin
  • obesity

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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