Dataset Information

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

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.

SUBMITTER: Sato T

PROVIDER: S-EPMC6479072 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Sato Tomoki T Watanabe Yui Y Nishimura Yuri Y Inoue Mizuki M Morita Akihito A Miura Shinji S

Biochemistry and biophysics reports 20190419

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 s ...[more]

PMID: 31032430

Similar Datasets

Project description:BackgroundPapillary thyroid carcinoma (PTC) is the most common thyroid malignancy, but little is known regarding PTC metabolic phenotypes and the effects of mitochondrial activity on PTC progression. The great potential of mitochondria-targeting therapy in cancer treatment promoted us to use tool compounds from a family of Mito-Fu derivatives to investigate how the regulation of mitochondrial respiration affected tumor progression characteristics and molecular changes in PTC.MethodsMito-Fu L20, a representative of 12 synthetic derivatives, was chosen for mitochondrial inhibition experiments. Sample sections from PTC patients were collected and processed to explore potential molecular alterations in tumor lymph node metastasis (LNM). In vitro analyses were performed using human PTC cell lines (K1 and TPC-1), with the human normal thyroid follicular cell line (Nthy) as a control. K1 cells were injected into nude mice to generate an animal model. The mice were injected with normal saline or Mito-Fu L20 at 20 or 50 mg/kg every other day; their body weights and tumor volumes were also measured over time. To elucidate the resulting metabolic phenotype, we measured oxygen consumption rate (OCR) and extracellular acidification rate (ECAR), cellular adenosine triphosphate (ATP) levels and reactive oxygen species (ROS) production, and mitochondrial membrane potential. Wound healing and Transwell assays, cell cycle assays, real-time fluorescence quantitative PCR, Western blotting, and immunohistochemical staining were performed to explore glycolysis-dominant metabolism in PTC.ResultsCyclin D1 and mitochondrial complex IV were detected in tumor samples from PTC patients with LNM. Mito-Fu L20 showed dose-independent and reversible modulation of mitochondrial respiration in PTC. In addition to mitochondrial dysfunction and early apoptosis, G1/S phase arrest. Notably, reversible mitochondrial inhibition yielded durable suppression of tumor proliferation, migration, and invasion via the PI3K/Akt/FoxO1/Cyclin D1 pathway. In vivo experiments demonstrated that Mito-Fu L20 has a good safety profile and specific restorative effect on mitochondrial activity in the liver. In addition, Mito-Fu L20 showed antitumor effects, alleviated tumor angiogenesis, and improved thyroid function.ConclusionReversible inhibition of ATP production and durable suppression of PTC growth indicates that the downregulation of mitochondrial function has a negative impact on tumor progression and LNM via the PI3K/Akt/FoxO1/Cyclin D1 pathway. The results provide new insights into the antitumor potential and clinical translation of mitochondrial inhibitors.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets