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This Article Full Text Full Text (PDF) All Versions of this Article: fj.08-108464v1 22/8/2981    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Perra, A. Articles by Columbano, A. PubMed PubMed Citation Articles by Perra, A. Articles by Columbano, A.

Thyroid hormone (T3) and TRβ agonist GC-1 inhibit/reverse nonalcoholic fatty liver in rats

Department of Toxicology, Oncology and Molecular Pathology Unit, University of Cagliari, Cagliari, Italy

¹Correspondence: Dipartimento di Tossicologia, Sezione di Oncologia e Patologia Molecolare, Via Porcell 4, 09124 Cagliari, Italy. E-mail: columbano{at}unica.it

Nonalcoholic fatty liver disease is the most common noninfectious liver disease in clinical practice, and there is an increasing need for new therapeutic approaches for the treatment of this liver disease. Here, we examined the effect of the thyroid hormone triiodothyronine (T3) and the agonist of the thyroid hormone receptor β isoform (TRβ), GC-1, on fatty liver and steatohepatitis induced in rodents by a choline-methionine deficient (CMD) diet. Male Fischer 344 rats fed a CMD diet for 1 wk developed a marked fatty liver and mild hepatitis. Concurrent administration of T3 resulted in a complete prevention of the fatty change associated with increased fatty acid mitochondrial and peroxisomal β-oxidation. To investigate whether T3 could also reverse fully established fatty liver, rats were fed a CMD diet for 10 wk and then cofed T3 for 1 wk. Coadministration of T3 resulted in a complete regression of liver steatosis associated with a decrease of lipid peroxidation, cyclooxygenase-2 expression, and activation of phospho-STAT3 and phospho-SAPK/JNK. Finally, additional experiments showed that GC-1, which has no significant side effects on heart rate, prevented and reverted CMD-induced fat accumulation, and ameliorated steatohepatitis. These results indicate that TR agonists have the potential to inhibit or reverse hepatic steatosis induced by a nutritional model.—Perra, A., Simbula, G., Simbula, M., Pibiri, M., Kowalik, M. A., Sulas, P., Cocco, M. T., Ledda-Columbano, G. M., Columbano, A. Thyroid hormone (T3) and TRβ agonist GC-1 inhibit/reverse nonalcoholic fatty liver in rats.

Key Words: hepatic steatosis • choline deficient diet • β-oxidation