Effect of Peripheral 5-HT on Glucose and Lipid Metabolism in Wether Sheep

Hitoshi Watanabe, Ryo Saito, Tatsuya Nakano, Hideyuki Takahashi, Yu Takahashi, Keisuke Sumiyoshi, Katsuyoshi Sato, Xiangning Chen, Natsumi Okada, Shunsuke Iwasaki, Dian W. Harjanti, Natsumi Sekiguchi, Hiroaki Sano, Haruki Kitazawa, Michael T. Rose, Shyuichi Ohwada, Kouichi Watanabe, Hisashi Aso, Hubert Vaudry (Editor)

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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.
Original languageEnglish
Article numbere88058
JournalPLoS One
Issue number2
Publication statusPublished - 04 Feb 2014


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