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Am J Physiol Regul Integr Comp Physiol 292: R1063-R1070, 2007. First published November 16, 2006; doi:10.1152/ajpregu.00699.2006
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APPETITE, OBESITY, DIGESTION, AND METABOLISM

Serotonin-type 3 receptors mediate intestinal lipid-induced satiation and Fos-like immunoreactivity in the dorsal hindbrain

David M. Savastano, Matthew R. Hayes, and Mihai Covasa

Department of Nutritional Sciences, College of Health and Human Development, The Pennsylvania State University, University Park, Pennsylvania

Submitted 2 October 2006 ; accepted in final form 8 November 2006

Several gastrointestinal stimuli, including some intestinal nutrients, have been shown to exert their satiating effect via activation of serotonin type-3 (5-HT3) receptors. The presence of lipids in the small intestine potently suppresses food intake; however, whether 5-HT3 receptors play a role in this response has not been directly examined. Therefore, using the selective 5-HT3 receptor antagonist ondansetron, we tested the hypothesis that duodenal infusion of lipid suppresses intake of both sucrose solution and chow through 5-HT3 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-HT3 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-HT3 receptors mediate both satiation, as well as hindbrain neuronal responses evoked by intestinal lipids.

food intake; lipids; intestinal chemoreception



Address for reprint requests and other correspondence: M. Covasa, Dept. of Nutritional Sciences, College of Health and Human Development, The Pennsylvania State Univ., 126 South Henderson, Univ. Park, PA, 16802 (E-mail: mzc13{at}psu.edu)




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From gut nutrient sensing to nutrient perception: a cooperative role involving CCK and 5-HT?
Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2007; 292(3): R1061 - R1062.
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