Acute fructose intake suppresses fasting-induced hepatic gluconeogenesis through the AKT-FoxO1 pathway

Tomoki Sato; Yui Watanabe; Yuri Nishimura; Mizuki Inoue; Akihito Morita; Shinji Miura

doi:10.1016/j.bbrep.2019.100638

Acute fructose intake suppresses fasting-induced hepatic gluconeogenesis through the AKT-FoxO1 pathway

Biochem Biophys Rep. 2019 Apr 19:18:100638. doi: 10.1016/j.bbrep.2019.100638. eCollection 2019 Jul.

Authors

Tomoki Sato^{1

2}, Yui Watanabe¹, Yuri Nishimura¹, Mizuki Inoue¹, Akihito Morita¹, Shinji Miura¹

Affiliations

¹ Laboratory of Nutritional Biochemistry, Graduate School of Nutritional and Environmental Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, 422-8526, Japan.
² Research Fellow of Japan Society for the Promotion of Science, 5-3-1 Kojimachi, Chiyoda-ku, Tokyo, 102-0083, Japan.

Abstract

Excessive intake of fructose increases lipogenesis in the liver, leading to hepatic lipid accumulation and development of fatty liver disease. Metabolic alterations in the liver due to fructose intake have been reported in many studies, but the effect of fructose administration on hepatic gluconeogenesis is not fully understood. The aim of this study was to evaluate the acute effects of fructose administration on fasting-induced hepatic gluconeogenesis. C57BL/6J mice were administered fructose solution after 14 h of fasting and plasma insulin, glucose, free fatty acids, and ketone bodies were analysed. We also measured phosphorylated AKT and forkhead box O (FoxO) 1 protein levels and gene expression related to gluconeogenesis in the liver. Furthermore, we measured glucose production from pyruvate after fructose administration. Glucose-administered mice were used as controls. Fructose administration enhanced phosphorylation of AKT in the liver, without increase of blood insulin levels. Blood free fatty acids and ketone bodies concentrations were as high as those in the fasting group after fructose administration, suggesting that insulin-induced inhibition of lipolysis did not occur in mice administered with fructose. Fructose also enhanced phosphorylation of FoxO1 and suppressed gluconeogenic gene expression, glucose-6-phosphatase activity, and glucose production from pyruvate. The present study suggests that acute fructose administration suppresses fasting-induced hepatic gluconeogenesis in an insulin-independent manner.

Keywords: AKT; CREB, cAMP response element binding protein; ChREBP, carbohydrate response element binding protein; EDTA, ethylenediaminetetraacetic acid; FFA, free fatty acid; FoxO, forkhead box O; FoxO1; Fructose; G6Pase; G6Pase, glucose-6-phosphatase; Gluconeogenesis; Insulin; PEPCK, phosphoenolpyruvate carboxykinase; PGC-1α, peroxisome proliferator-activated receptor gamma coactivator-1 alpha; PI3K, phosphoinositide-3-kinase; PIP 3, phosphatidylinositol-(3,4,5)-trisphosphate; SREBP, sterol-regulatory element binding protein.