The ameliorating effect of rosiglitazone on experimental nonalcoholic steatohepatitis is associated with regulating adiponectin receptor expression in rats

Although nonalcoholic steatohepatitis (NASH) is associated with insulin resistance partly due to reduced levels of circulating adiponectin the role of adiponectin receptors including adiponectin receptor 1 and adiponectin receptor 2 in adipose tissues in NASH remains controversial The present study showed that there was a marked decline in adiponectin receptor 1 and adiponectin receptor 2 expressions in liver and visceral fat and these expressions were elevated in muscle of NASH rats 12 weeks after oral administration of a high-fat diet An 8 week continuous treatment with rosiglitazone a peroxisome proliferator-activated receptors gamma (PPAR gamma) agonist improved the histological lesions markedly in liver of NASH rats and concurrently increased mRNA and protein expressions of adiponectin receptor 1 and adiponectin receptor 2 in liver and visceral fat with down regulation of the two receptors in muscle There was a negative correlation between the ratio of adiponectin receptors/beta actin protein and serum TNF-alpha in the liver and visceral fat and a positive correlation in muscle Additionally rosiglitazone increased circulating adiponectin which was negatively correlated with serum TNF-a These results indicated that rosiglitazone improved NASH by directly modulating adiponectin receptor 1 and adiponectin receptor 2 in various adipose tissues or indirectly possibly via decreasing serum TNF alpha (C) 2010 Elsevier BV All rights reserved