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. The insulin-sensitizing thiazolidinediones enhance glucose disposal in skeletal muscle and have been reported to increase the expression of uncoupling proteins in various experimental systems. We therefore studied the effect of troglitazone treatment on UCP3 gene expression in muscles from lean and obese Zucker rats. In comparison with obese littermates, basal UCP3 mRNA levels 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 muscles of obese littermates (all P<0.001). The troglitazone-dependent decrease in UCP3 gene expression was accompanied by an increased weight gain in obese rats, while no such effect was observed in lean rats. In obese rats, improvement of insulin resistance by troglitazone was associated with increased rates of basal and insulin-stimulated CO(2) production from glucose measured in soleus muscle. These studies demonstrate that effects of troglitazone on UCP3 gene expression depend on the phenotype of Zucker rats and that troglitazone-induced metabolic improvements are not related to increased uncoupling resulting from upregulation of UCP3 mRNA expression in muscle.
Oberkofler
H
H
Department of Laboratory Medicine, Landeskrankenanstalten, Salzburg, Austria.
Neschen
S
S
Esterbauer
H
H
Waldhäusl
W
W
Patsch
W
W
Fürnsinn
C
C
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001835:Body Weight; D002245:Carbon Dioxide / Q000032:analysis; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics*; D002839:Chromans / Q000494:pharmacology*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000378:metabolism; D004195:Disease Models, Animal; D004734:Energy Metabolism; D005227:Fatty Acids / Q000097:blood / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D007333:Insulin Resistance; D007473:Ion Channels; D024101:Mitochondrial Proteins; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011924:Rats, Zucker; D013844:Thiazoles / Q000494:pharmacology*; D045162:Thiazolidinediones; D000077288:Troglitazone; D000071247:Uncoupling Protein 3
D000975:Antioxidants; D002352:Carrier Proteins; D002839:Chromans; D005227:Fatty Acids; D007473:Ion Channels; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; D013844:Thiazoles; D045162:Thiazolidinediones; C000604394:Ucp3 protein, rat; D000071247:Uncoupling Protein 3; D002245:Carbon Dioxide; D000077288:Troglitazone; D005947:Glucose