%0 Journal Article %T Effect of Peripheral 5-HT on Glucose and Lipid Metabolism in Wether Sheep %A Hitoshi Watanabe %A Ryo Saito %A Tatsuya Nakano %A Hideyuki Takahashi %A Yu Takahashi %A Keisuke Sumiyoshi %A Katsuyoshi Sato %A Xiangning Chen %A Natsumi Okada %A Shunsuke Iwasaki %A Dian W. Harjanti %A Natsumi Sekiguchi %A Hiroaki Sano %A Haruki Kitazawa %A Michael T. Rose %A Shyuichi Ohwada %A Kouichi Watanabe %A Hisashi Aso %J PLOS ONE %D 2014 %I Public Library of Science (PLoS) %R 10.1371/journal.pone.0088058 %X In mice, peripheral 5-HT induces an increase in the plasma concentrations of glucose, insulin and bile acids, and a decrease in plasma triglyceride, NEFA and cholesterol concentrations. However, given the unique characteristics of the metabolism of ruminants relative to monogastric animals, the physiological role of peripheral 5-HT on glucose and lipid metabolism in sheep remains to be established. Therefore, in this study, we investigated the effect of 5-HT on the circulating concentrations of metabolites and insulin using five 5-HT receptor (5HTR) antagonists in sheep. After fasting for 24 h, sheep were intravenously injected with 5-HT, following which-, plasma glucose, insulin, triglyceride and NEFA concentrations were significantly elevated. In contrast, 5-HT did not affect the plasma cholesterol concentration, and it induced a decrease in bile acid concentrations. Increases in plasma glucose and insulin concentrations induced by 5-HT were attenuated by pre-treatment with Methysergide, a 5HTR 1, 2 and 7 antagonist. Additionally, decreased plasma bile acid concentrations induced by 5-HT were blocked by pre-treatment with Ketanserin, a 5HTR 2A antagonist. However, none of the 5HTR antagonists inhibited the increase in plasma triglyceride and NEFA levels induced by 5-HT. On the other hand, mRNA expressions of 5HTR1D and 1E were observed in the liver, pancreas and skeletal muscle. These results suggest that there are a number of differences in the physiological functions of peripheral 5-HT with respect to lipid metabolism between mice and sheep, though its effect on glucose metabolism appears to be similar between these species. %U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0088058