2026-04-17T05:37:27Zhttps://recercat.cat/oai/request

oai:recercat.cat:2445/539462025-12-05T14:21:54Zcom_2072_1057col_2072_478816col_2072_478917

00925njm 22002777a 4500 dc Rebollo de Grado, Alba author Roglans i Ribas, Núria author Baena Muñoz, Miguel author Padrosa, Anna author Sánchez Peñarroya, Rosa M. author Merlos Roca, Manuel author Alegret i Jordà, Marta author Laguna Egea, Juan Carlos author 2014-05-09T11:17:33Z 2014-05-09T11:17:33Z 2014-02 2014-05-09T11:17:33Z 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 kinase (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. Resistència a la insulina Fetge Fructosa Insulin resistance Liver Fructose Liquid fructose down-regulates liver insulin receptor substrate 2 and gluconeogeneic enzymes by modifying nutrient sensing factors in rats