Effect of PPAR-Γ agonist-rosiglitazone-on adiponectin level in the metabolic syndrome

The metabolic syndrome is associated with significant cardiovascular morbidity and mortality. Adiponectin is an adipocytokine that possesses anti-diabetic, anti-atherogenic and anti-inflammatory properties which collectively establish its unique vascular protective role. In addition, thiazolidinediones (TZDs) improve glucose tolerance and insulin sensitivity in animal models of insulin resistance. Therefore we studied the effect of rosiglitazone on adiponectin levels in the fructose-induced hypertensive, hyperinsulinemic, hypertriglyceridemic rat model. 20 male Sprague-Dawley rats were fed a fructose-enriched diet for 3 weeks.Ten rats continued to consume the Fructose diet for another 2 weeks, while the other 10 received rosiglitazone (10mg/kg) in their drinking water on top of the fructose. Blood pressure (BP), oral glucose tolerance test (OGTT), plasma insulin, triglycerides and adiponectin levels were measured at baseline, after 3 weeks and at the end of the experiment. Visceral fat tissues were taken from all animals after 5 weeks and the expression of adiponectin mRNA was determined by quantitative RT-PCR. Fructose feeding led to significant increase in BP, insulin and triglyceride levels and to impaired OGTT. Adiponectin plasma level did not change significantly. Treatment with rosiglitazone, however, lowered BP, improved OGTT and resulted in significant increase in adiponectin plasma level (from 5.9±2.2 to 18.3±5μg/ml). Adiponectin mRNA expression in visceral fat increased 3.5 fold following rosiglitazone treatment. This study shows for the first time in an animal model which displays most of the metabolic syndrome components, that the insulin sensitizer rosiglitazone induced elevation of plasma level of adiponectin due to an increase in gene expression. Whether this is the mechanism through which rosiglitazone exerts its beneficial effect remains to be studied.