UCP3 gene expression does not correlate with muscle oxidation rates in troglitazone-treated Zucker fatty rats

Uncoupling protein-3 (UCP3), a mitochondrial carrier protein predominantly expressed in muscle, has been suggested to release stored energy as heat. T he insulin-sensitizing thiazolidinediones enhance glucose disposal in skele tal muscle and have been reported to increase the expression of uncoupling proteins in various experimental systems. We therefore studied the effect o f troglitazone treatment on UCP3 gene expression in muscles from lean and o bese Zucker rats. In comparison with obese littermates, basal UCP3 mRNA lev els in lean Zucker rats tended to be higher in white and red gastrocnemius muscles, but were lower in soleus (P < 0.001) muscle and heart (P < 0.01), In lean rats, troglitazone significantly increased UCP3 gene expression in white and red gastrocnemius and heart muscles (all P < 0.01). In contrast, the drug reduced UCP3 mRNA expression in red gastrocnemius and soleus muscl es of obese littermates tall P < 0.001). The troglitazone-dependent decreas e in UCP3 gene expression was accompanied by an increased weight gain in ob ese rats, while no such effect was observed in lean rats. In obese rats, im provement of insulin resistance by troglitazone was associated with increas ed rates of basal and insulin stimulated CO2 production from glucose measur ed in soleus muscle. These studies demonstrate that effects of troglitazone on UCP3 gene expression depend on the phenotype of Zucker rats and that tr oglitazone-induced metabolic improvements are not related to increased unco upling resulting from upregulation of UCP3 mRNA expression in muscle. (C) 2 000 Elsevier Science B.V. All rights reserved.