Serotonin-type 3 receptors mediate intestinal lipid-induced satiation and Fos-like immunoreactivity in the dorsal hindbrain.
Several gastrointestinal stimuli, including some intestinal nutrients, have been shown to exert their satiating effect via activation of serotonin type-3 (5-HT(3)) receptors. The presence of lipids in the small intestine potently suppresses food intake; however, whether 5-HT(3) receptors play a role in this response has not been directly examined. Therefore, using the selective 5-HT(3) receptor antagonist ondansetron, we tested the hypothesis that duodenal infusion of lipid suppresses intake of both sucrose solution and chow through 5-HT(3) receptor activation. Rats duodenally infused with 72 and 130 mM Intralipid suppressed 1-h 15% sucrose intake by 33 and 67%, respectively. Suppression of sucrose intake by 72 mM Intralipid was significantly attenuated by ondansetron at all doses tested (0.5, 1.0, 2.0, and 5.0 mg/kg ip), whereas the lowest effective dose of ondansetron to attenuate suppression of intake by 130 mM Intralipid was 1.0 mg/kg. Furthermore, infusion of 130 mM Intralipid suppressed 1- and 4-h chow intake by 35 and 20%, respectively. Ondansetron administered as low as 0.5 mg/kg significantly attenuated 1-h Intralipid-induced suppression of chow intake and completely reversed the suppression by 4 h. Administration of ondansetron alone did not alter sucrose or chow intake compared with vehicle injection at any time. Finally, to test whether Intralipid-induced neuronal activation of the dorsal vagal complex is mediated by 5-HT(3) receptors, Fos-like immunoreactivity (Fos-LI) was quantified in ondansetron-pretreated rats following intestinal lipid infusion. Ondansetron (1 mg/kg) significantly attenuated duodenal intralipid-induced Fos-LI in the dorsal hindbrain. These data support the hypothesis that 5-HT(3) receptors mediate both satiation, as well as hindbrain neuronal responses evoked by intestinal lipids.
Savastano
David M
DM
Department of Nutritional Sciences, College of Health and Human Development, The Pennsylvania State University, 126 South Henderson, University Park, PA 16802, USA.
Hayes
Matthew R
MR
Covasa
Mihai
M
D000818:Animals; D031608:Area Postrema / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005217:Fat Emulsions, Intravenous / Q000008:administration & dosage; D007150:Immunohistochemistry; D007262:Infusions, Intravenous; D007276:Injections, Intraventricular; D007421:Intestine, Small / Q000187:drug effects / Q000502:physiology*; D008055:Lipids / Q000008:administration & dosage; D008297:Male; D017294:Ondansetron / Q000008:administration & dosage / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044406:Receptors, Serotonin, 5-HT3 / Q000187:drug effects / Q000502:physiology*; D012249:Rhombencephalon / Q000502:physiology*; D012528:Satiety Response / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D017552:Solitary Nucleus / Q000187:drug effects; D013395:Sucrose / Q000008:administration & dosage / Q000378:metabolism; D000099169:Fos-Related Antigen 1
D005217:Fat Emulsions, Intravenous; D008055:Lipids; D017294:Ondansetron; D016760:Proto-Oncogene Proteins c-fos; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists; D013395:Sucrose; D000099169:Fos-Related Antigen 1