Nucleus of the Solitary Tract Serotonin 5-HT2C Receptors Modulate Food Intake
d'Agostino, Giuseppe | Lyons, David | Cristiano, Claudia | Lettieri, Miriam | Olarte-Sanchez, Cristian | Burke, Luke | Greenwald-Yarnell, Megan | Cansell, Céline | Doslikova, Barbora | Georgescu, Teodora | Martinez de Morentin, Pablo Blanco | Myers, Martin | Rochford, Justin | Heisler, Lora | University of Aberdeen | University of Cambridge [UK] (CAM) | University of Michigan [Ann Arbor] ; University of Michigan System
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Показать больше [+] Меньше [-]Английский. 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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