Nucleus of the Solitary Tract Serotonin 5-HT2C Receptors Modulate Food Intake

Giuseppe d'Agostino (Corresponding Author), David Lyons, Claudia Cristiano, Miriam Lettieri, Cristian Olarte-Sanchez, Luke K. Burke, Megan Greenwald-Yarnell, Celine Cansell, Barbora Doslikova, Teodora Georgescu, Pablo Blanco Martinez de Morentin, Martin G Myers Jr., Justin J. Rochford, Lora Heisler (Corresponding Author)

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Abstract

To meet the challenge to human health posed by obesity, a better understanding of the regulation of feeding is essential. Medications targeting 5-hydroxytryptamine (5-HT; serotonin) 2C receptors (htr2c; 5-HT2CR) improve obesity. Here we probed the functional significance of 5-HT2CRs specifically within the brainstem nucleus of the solitary tract (5-HT2CRNTS) in feeding behavior. Selective activation of 5-HT2CRNTS decreased feeding and was sufficient to mediate acute food intake reductions elicited by the 5-HT2CR agonist obesity medication lorcaserin. Similar to pro-opiomelanocortin neurons expressed within the hypothalamic arcuate nucleus (POMCARC), a subset of POMCNTS neurons co-expressed 5-HT2CRs and were activated by 5-HT2CR agonists. Knockdown of POMCNTS prevented the acute appetite-suppressive effect of lorcaserin, whereas POMCARC knockdown prevented the full anorectic effect. These data identify 5-HT2CRNTS as a sufficient subpopulation of 5-HT2CRs in reducing food intake when activated and reveal that 5-HT2CR agonist obesity medications require POMC within the NTS and ARC to reduce food intake.
Original languageEnglish
Pages (from-to)619.-630.e5
Number of pages18
JournalCell Metabolism
Volume28
Issue number4
Early online date23 Aug 2018
DOIs
Publication statusPublished - 2 Oct 2018

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Keywords

  • serotonin
  • 5-HT2CR
  • lorcaserin
  • food intake
  • nucleus of the solitary tract
  • obesity

Cite this

d'Agostino, G., Lyons, D., Cristiano, C., Lettieri, M., Olarte-Sanchez, C., Burke, L. K., Greenwald-Yarnell, M., Cansell, C., Doslikova, B., Georgescu, T., Blanco Martinez de Morentin, P., Myers Jr., M. G., Rochford, J. J., & Heisler, L. (2018). Nucleus of the Solitary Tract Serotonin 5-HT2C Receptors Modulate Food Intake. Cell Metabolism, 28(4), 619.-630.e5. https://doi.org/10.1016/j.cmet.2018.07.017