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

Journal Article · Tue Feb 15 00:00:00 EST 2011 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2010.11.011· OSTI ID:21535235

Vila, Laia; Rebollo, Alba; Adalsteisson, Gunnar S ^[1]; Alegret, Marta; Merlos, Manuel; Roglans, Nuria ^[1]; CIBERobn, ^[2]; CIBERobn, ^[2]

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1. Pharmacology Unit, Department of Pharmacology and Therapeutic Chemistry, School of Pharmacy, University of Barcelona, Barcelona (Spain)
2. Center for Biomedical Investigation Network in Obesity and Nutrition Physiopathology; Spain

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

• OSTI ID: 21535235
• Journal Information: Toxicology and Applied Pharmacology, Vol. 251, 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.; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

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