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

Aug 28, 2018Cell metabolism

Serotonin 5-HT2C Receptors in a Brain Area Controlling Internal Signals Influence Food Intake

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Abstract

Selective activation of 5-HT receptors in the brainstem nucleus of the solitary tract decreased feeding.

5-HT receptor activation may mediate reductions in food intake associated with the obesity medication lorcaserin.
A subset of pro-opiomelanocortin neurons in the hypothalamic arcuate nucleus co-expressed 5-HT receptors and responded to agonists.
Knockdown of pro-opiomelanocortin neurons inhibited the appetite-suppressive effects of lorcaserin.
5-HT receptor activation in specific brain regions is linked to reduced food intake.

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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-HTR) improve obesity. Here we probed the functional significance of 5-HTRs specifically within the brainstem nucleus of the solitary tract (5-HTR) in feeding behavior. Selective activation of 5-HTRdecreased feeding and was sufficient to mediate acute food intake reductions elicited by the 5-HTR agonist obesity medication lorcaserin. Similar to pro-opiomelanocortin neurons expressed within the hypothalamic arcuate nucleus (POMC), a subset of POMCneurons co-expressed 5-HTRs and were activated by 5-HTR agonists. Knockdown of POMCprevented the acute appetite-suppressive effect of lorcaserin, whereas POMCknockdown prevented the full anorectic effect. These data identify 5-HTRas a sufficient subpopulation of 5-HTRs in reducing food intake when activated and reveal that 5-HTR agonist obesity medications require POMC within the NTS and ARC to reduce food intake. 2C2C2C2C2C2C2C2C2C2C NTS NTS ARC NTS NTS ARC NTS

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

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