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  • Title: Nucleus of the Solitary Tract Serotonin 5-HT2C Receptors Modulate Food Intake.
    Author: D'Agostino G, Lyons D, Cristiano C, Lettieri M, Olarte-Sanchez C, Burke LK, Greenwald-Yarnell M, Cansell C, Doslikova B, Georgescu T, Martinez de Morentin PB, Myers MG, Rochford JJ, Heisler LK.
    Journal: Cell Metab; 2018 Oct 02; 28(4):619-630.e5. PubMed ID: 30146485.
    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.
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