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

Fingerprint

Receptor, Serotonin, 5-HT2C
Solitary Nucleus
Obesity
Eating
Pro-Opiomelanocortin
AIDS-Related Complex
Neurons
Appetite Depressants
Arcuate Nucleus of Hypothalamus
Feeding Behavior
Appetite
Brain Stem
Serotonin
Health
lorcaserin

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., ... 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

Nucleus of the Solitary Tract Serotonin 5-HT2C Receptors Modulate Food Intake. / d'Agostino, Giuseppe (Corresponding Author); Lyons, David; Cristiano, Claudia; Lettieri, Miriam; Olarte-Sanchez, Cristian; Burke, Luke K.; Greenwald-Yarnell, Megan; Cansell, Celine; Doslikova, Barbora; Georgescu, Teodora; Blanco Martinez de Morentin, Pablo; Myers Jr., Martin G; Rochford, Justin J.; Heisler, Lora (Corresponding Author).

In: Cell Metabolism, Vol. 28, No. 4, 02.10.2018, p. 619.-630.e5.

Research output: Contribution to journalArticle

d'Agostino, G, Lyons, D, Cristiano, C, Lettieri, M, Olarte-Sanchez, C, Burke, LK, Greenwald-Yarnell, M, Cansell, C, Doslikova, B, Georgescu, T, Blanco Martinez de Morentin, P, Myers Jr., MG, Rochford, JJ & Heisler, L 2018, 'Nucleus of the Solitary Tract Serotonin 5-HT2C Receptors Modulate Food Intake', Cell Metabolism, vol. 28, no. 4, pp. 619.-630.e5. https://doi.org/10.1016/j.cmet.2018.07.017
d'Agostino G, Lyons D, Cristiano C, Lettieri M, Olarte-Sanchez C, Burke LK et al. Nucleus of the Solitary Tract Serotonin 5-HT2C Receptors Modulate Food Intake. Cell Metabolism. 2018 Oct 2;28(4):619.-630.e5. https://doi.org/10.1016/j.cmet.2018.07.017
d'Agostino, Giuseppe ; Lyons, David ; Cristiano, Claudia ; Lettieri, Miriam ; Olarte-Sanchez, Cristian ; Burke, Luke K. ; Greenwald-Yarnell, Megan ; Cansell, Celine ; Doslikova, Barbora ; Georgescu, Teodora ; Blanco Martinez de Morentin, Pablo ; Myers Jr., Martin G ; Rochford, Justin J. ; Heisler, Lora. / Nucleus of the Solitary Tract Serotonin 5-HT2C Receptors Modulate Food Intake. In: Cell Metabolism. 2018 ; Vol. 28, No. 4. pp. 619.-630.e5.
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AU - Burke, Luke K.

AU - Greenwald-Yarnell, Megan

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KW - 5-HT2CR

KW - lorcaserin

KW - food intake

KW - nucleus of the solitary tract

KW - obesity

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