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Reduction of liver fructokinase expression and improved hepatic inflammation and metabolism in liquid fructose-fed rats after atorvastatin treatment

Abstract

Consumption of beverages that contain fructose favors the increasing prevalence of metabolic syndrome alterations in humans, including non-alcoholic fatty liver disease (NAFLD). Although the only effective treatment for NAFLD is caloric restriction and weight loss, existing data show that atorvastatin, a hydroxymethyl-glutaryl-CoA reductase inhibitor, can be used safely in patients with NAFLD and improves hepatic histology. To gain further insight into the molecular mechanisms of atorvastatin's therapeutic effect on NAFLD, we used an experimental model that mimics human consumption of fructose-sweetened beverages. Control, fructose (10% w/v solution) and fructose + atorvastatin (30 mg/kg/day) Sprague-Dawley rats were sacrificed after 14 days. Plasma and liver tissue samples were obtained to determine plasma analytes, liver histology, and the expression of liver proteins that are related to fatty acid synthesis and catabolism, and inflammatory processes. Fructose supplementation induced hypertriglyceridemia and hyperleptinemia, hepatic steatosis and necroinflammation, increased the expression of genes related to fatty acid synthesis and decreased fatty acid {beta}-oxidation activity. Atorvastatin treatment completely abolished histological signs of necroinflammation, reducing the hepatic expression of metallothionein-1 and nuclear factor kappa B binding. Furthermore, atorvastatin reduced plasma (x 0.74) and liver triglyceride (x 0.62) concentrations, decreased the liver expression of carbohydrate response element binding protein transcription  More>>
Authors:
Publication Date:
Feb 15, 2011
Product Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 251; Journal Issue: 1; Other Information: DOI: 10.1016/j.taap.2010.11.011; PII: S0041-008X(10)00443-6; Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.
Subject:
60 APPLIED LIFE SCIENCES; BEVERAGES; CARBOXYLIC ACIDS; CATABOLISM; CONTROL; DISEASES; ENZYMES; FRUCTOSE; GENES; HISTOLOGY; HUMAN POPULATIONS; INFLAMMATION; INGESTION; LIVER; METALLOTHIONEIN; OXIDATION; PATIENTS; RATS; SYNTHESIS; TRANSCRIPTION FACTORS; TRIGLYCERIDES; ANIMALS; BODY; CARBOHYDRATES; CHEMICAL REACTIONS; DIGESTIVE SYSTEM; ESTERS; FOOD; GLANDS; HEXOSES; INTAKE; KETONES; LIPIDS; MAMMALS; METABOLISM; METALLOPROTEINS; MONOSACCHARIDES; ORGANIC ACIDS; ORGANIC COMPOUNDS; ORGANS; PATHOLOGICAL CHANGES; POPULATIONS; PROTEINS; RODENTS; SACCHARIDES; SYMPTOMS; VERTEBRATES
OSTI ID:
21535235
Country of Origin:
United States
Language:
English
Other Identifying Numbers:
Journal ID: ISSN 0041-008X; TXAPA9; TRN: US11R1417014184
Availability:
Available from http://dx.doi.org/10.1016/j.taap.2010.11.011
Submitting Site:
INIS
Size:
page(s) 32-40
Announcement Date:
Mar 19, 2012

Citation Formats

Vila, Laia, Rebollo, Alba, Adalsteisson, Gunnar S, Alegret, Marta, Merlos, Manuel, Roglans, Nuria, IBUB - Institute of Biomedicine, University of Barcelona, Barcelona (Spain), CIBERobn,, Laguna, Juan C., E-mail: jclagunae@ub.edu [Pharmacology Unit, Department of Pharmacology and Therapeutic Chemistry, School of Pharmacy, University of Barcelona, Barcelona (Spain), IBUB -Institute of Biomedicine, University of Barcelona, Barcelona (Spain), and CIBERobn,. Reduction of liver fructokinase expression and improved hepatic inflammation and metabolism in liquid fructose-fed rats after atorvastatin treatment. United States: N. p., 2011. Web. doi:10.1016/j.taap.2010.11.011.
Vila, Laia, Rebollo, Alba, Adalsteisson, Gunnar S, Alegret, Marta, Merlos, Manuel, Roglans, Nuria, IBUB - Institute of Biomedicine, University of Barcelona, Barcelona (Spain), CIBERobn,, Laguna, Juan C., E-mail: jclagunae@ub.edu [Pharmacology Unit, Department of Pharmacology and Therapeutic Chemistry, School of Pharmacy, University of Barcelona, Barcelona (Spain), IBUB -Institute of Biomedicine, University of Barcelona, Barcelona (Spain), & CIBERobn,. Reduction of liver fructokinase expression and improved hepatic inflammation and metabolism in liquid fructose-fed rats after atorvastatin treatment. United States. doi:10.1016/j.taap.2010.11.011.
Vila, Laia, Rebollo, Alba, Adalsteisson, Gunnar S, Alegret, Marta, Merlos, Manuel, Roglans, Nuria, IBUB - Institute of Biomedicine, University of Barcelona, Barcelona (Spain), CIBERobn,, Laguna, Juan C., E-mail: jclagunae@ub.edu [Pharmacology Unit, Department of Pharmacology and Therapeutic Chemistry, School of Pharmacy, University of Barcelona, Barcelona (Spain), IBUB -Institute of Biomedicine, University of Barcelona, Barcelona (Spain), and CIBERobn,. 2011. "Reduction of liver fructokinase expression and improved hepatic inflammation and metabolism in liquid fructose-fed rats after atorvastatin treatment." United States. doi:10.1016/j.taap.2010.11.011. https://www.osti.gov/servlets/purl/10.1016/j.taap.2010.11.011.
@misc{etde_21535235,
title = {Reduction of liver fructokinase expression and improved hepatic inflammation and metabolism in liquid fructose-fed rats after atorvastatin treatment}
author = {Vila, Laia, Rebollo, Alba, Adalsteisson, Gunnar S, Alegret, Marta, Merlos, Manuel, Roglans, Nuria, IBUB - Institute of Biomedicine, University of Barcelona, Barcelona (Spain), CIBERobn,, Laguna, Juan C., E-mail: jclagunae@ub.edu [Pharmacology Unit, Department of Pharmacology and Therapeutic Chemistry, School of Pharmacy, University of Barcelona, Barcelona (Spain), IBUB -Institute of Biomedicine, University of Barcelona, Barcelona (Spain), and CIBERobn,}
abstractNote = {Consumption of beverages that contain fructose favors the increasing prevalence of metabolic syndrome alterations in humans, including non-alcoholic fatty liver disease (NAFLD). Although the only effective treatment for NAFLD is caloric restriction and weight loss, existing data show that atorvastatin, a hydroxymethyl-glutaryl-CoA reductase inhibitor, can be used safely in patients with NAFLD and improves hepatic histology. To gain further insight into the molecular mechanisms of atorvastatin's therapeutic effect on NAFLD, we used an experimental model that mimics human consumption of fructose-sweetened beverages. Control, fructose (10% w/v solution) and fructose + atorvastatin (30 mg/kg/day) Sprague-Dawley rats were sacrificed after 14 days. Plasma and liver tissue samples were obtained to determine plasma analytes, liver histology, and the expression of liver proteins that are related to fatty acid synthesis and catabolism, and inflammatory processes. Fructose supplementation induced hypertriglyceridemia and hyperleptinemia, hepatic steatosis and necroinflammation, increased the expression of genes related to fatty acid synthesis and decreased fatty acid {beta}-oxidation activity. Atorvastatin treatment completely abolished histological signs of necroinflammation, reducing the hepatic expression of metallothionein-1 and nuclear factor kappa B binding. Furthermore, atorvastatin reduced plasma (x 0.74) and liver triglyceride (x 0.62) concentrations, decreased the liver expression of carbohydrate response element binding protein transcription factor (x0.45) and its target genes, and increased the hepatic activity of the fatty acid {beta}-oxidation system (x 1.15). These effects may be related to the fact that atorvastatin decreased the expression of fructokinase (x 0.6) in livers of fructose-supplemented rats, reducing the metabolic burden on the liver that is imposed by continuous fructose ingestion. - Graphical Abstract: Display Omitted Research Highlights: >Fructose administration as a liquid solution to Sprague-Dawley male rats induced hypertriglyceridemia, hyperleptinemia, hepatic steatosis and necroinflammation. >Atorvastatin administration: >Abolished histological sings of necroinflammation and reduced plasma and liver triglyceride concentrations. >Reduced the expression of phospho-I{kappa}B >Reduced the expression of fructokinase, a key enzyme controlling fructose metabolism}
doi = {10.1016/j.taap.2010.11.011}
journal = {Toxicology and Applied Pharmacology}
issue = {1}
volume = {251}
place = {United States}
year = {2011}
month = {Feb}
}