T-3 increases mitochondrial ATP production in oxidative muscle despite increased expression of UCP2 and-3

Triiodothyronine (T-3) increases O-2 and nutrient flux through mitochondria (Mito) of many tissues, but it is unclear whether ATP synthesis is increas ed, particularly in different types of skeletal muscle, because variable ch anges in uncoupling proteins (UCP) and enzymes have been reported. Thus Mit e ATP production was measured in oxidative and glycolytic muscles, as well as in liver and heart, in rats administered T-3 for 14 days. Relative to sa line-treated controls, T-3 rats had 80, 168, and 62% higher ATP production in soleus muscle, liver, and heart, respectively, as well as higher activit ies of citrate synthase (CS; 63, 90, 25%) and cytochrome c oxidase (COX; 11 9, 225, 52%) in the same tissues (all P < 0.01). In plantaris muscle of T-3 rats, CS was only slightly higher (17%, P < 0.05) than in controls, and AT P production and COX were unaffected. mRNA levels of COX I and III were 33 and 47% higher in soleus of T-3 rats (P < 0.01), but there were no differen ces in plantaris. In contrast, UCP2 and -3 mRNAs were 2.5- to 14-fold highe r, and protein levels were 3- to 10-fold higher in both plantaris and soleu s of the T-3 group. We conclude that T-3 increases oxidative enzymes and Mi te ATP production and Mite-encoded transcripts in oxidative but not glycoly tic rodent tissues. Despite large increases in UCP expression, ATP producti on was enhanced in oxidative tissues and maintained in glycolytic muscle of hyperthyroid rats.