Title: Effect of Rosiglitazone on Liver Structure and Function in Genetically Diabetic Akita Mice
Authors: Hemmeryckx, Bianca ×
Gaekens, Marijke
Gallacher, David J.
Lu, Hua Rong
Lijnen, Roger #
Issue Date: 11-Jul-2013
Publisher: Nordic Pharmacological Society
Series Title: Basic & Clinical Pharmacology & Toxicology vol:113 issue:5 pages:353-360
Abstract: Genetically diabetic Akita mice, kept on a high-fat and high-cholesterol diet, and treated with the peroxisome proliferator-activated receptor-γ agonist rosiglitazone (10 mg/kg per day during 4 months), displayed rosiglitazone-induced side effects, similar to those observed in patients, including weight and fat gain and early signs of hypertrophic cardiomyopathy. As several cases of hepatotoxicity were reported in patients receiving rosiglitazone treatment, this study evaluated whether rosiglitazone also induced hepatotoxicity in these diabetic animals. Liver structure and function was analysed in wild-type and rosiglitazone-treated and untreated Akita mice, kept for 4 months on the high-fat and high-cholesterol diet. Decreased circulating levels of the liver enzymes aspartate and alanine aminotransferase and increased levels of alkaline phosphatases were observed upon rosiglitazone treatment, whereas liver weight was markedly increased. Rosiglitazone administration was associated with liver steatosis, as demonstrated by triglyceride accumulation. However, gene expression of steatosis markers in liver tissue was not markedly affected by rosiglitazone treatment, while expression of fatty acid transport protein was reduced by rosiglitazone treatment, suggesting an impairment of the fatty acid β-oxidation pathway. mRNA expression of pro- and anti-oxidant enzymes and liver 3-nitrotyrosine content was not affected. Furthermore, gene and protein expression of macrophage markers and of cell adhesion molecules did not indicate progression to steatohepatitis, whereas an unaltered collagen deposition did not suggest steatofibrosis. In conclusion, rosiglitazone treatment of diabetic Akita mice induced liver steatosis without, however, progression to more advanced stages of liver disease.
ISSN: 1742-7835
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Molecular and Vascular Biology
× corresponding author
# (joint) last author

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