期刊
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
卷 25, 期 2, 页码 250-258出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jnutbio.2013.10.014
关键词
Insulin resistance; FoxO1; XBP-1; SIRT1; p38-MAPK; mTOR
资金
- Fundacio Privada Catalana de Nutricio i Lipids
- Ministerio de Economia y Competitividad [SAF2010-15664]
- European Union FEDER funds
- Fondo Investigaciones Sanitarias/Instituto de Salud Carlos III
- FPI-MICINN grant from the Spanish Ministry of Science and Innovation
High consumption of fructose-sweetened beverages has been linked to a high prevalence of chronic metabolic diseases. We have previously shown that a short course of fructose supplementation as a liquid solution induces glucose intolerance in female rats. In the present work, we characterized the fructose-driven changes in the liver and the molecular pathways involved. To this end, female rats were supplemented or not with liquid fructose (10%, w/v) for 7 or 14 days. Glucose and pyruvate tolerance tests were performed, and the expression of genes related to insulin signaling, gluconeogenesis and nutrient sensing pathways was evaluated. Fructose-supplemented rats showed increased plasma glucose excursions in glucose and pyruvate tolerance tests and reduced hepatic expression of several genes related to insulin signaling, including insulin receptor substrate 2 (IRS-2). However, the expression of key gluconeogenic enzymes, glucose-6-phosphatase and phosphoenolpyruvate carboxykinase, was reduced. These effects were caused by an inactivation of hepatic forkhead box O1 (FoxO1) due to an increase in its acetylation state driven by a reduced expression and activity of sirtuin 1 (SIRT1). Further contributing to FoxO1 inactivation, fructose consumption elevated liver expression of the spliced form of X-box-binding-protein-1 as a consequence of an increase in the activity of the mammalian target of rapamycin 1 and protein 38-mitogen activated protein lcinase (p38-MAPK). Liquid fructose affects both insulin signaling (IRS-2 and FoxO1) and nutrient sensing pathways (p38-MAPK, mTOR and SIRT1), thus disrupting hepatic insulin signaling without increasing the expression of key gluconeogenic enzymes. (C) 2014 Elsevier Inc. All rights reserved.
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