The Regulation of Oxidative Metabolism

Short, Kevin R., Jonas Nygren, Rocco Barazzoni, James Levine, and K. Sreekumaran Nair. T3 increases mitochondrial ATP production in oxidative muscle despite increased expression of UCP2 and -3. Am J Physiol Endocrinol Metab 280: E761–E769, 2001.—Triiodothyronine (T3) increases O2 and nutrient flux through mitochondria (Mito) of many tissues, but it is unclear whether ATP synthesis is increased, particularly in different types of skeletal muscle, because variable changes in uncoupling proteins (UCP) and enzymes have been reported. Thus Mito ATP production was measured in oxidative and glycolytic muscles, as well as in liver and heart, in rats administered T3 for 14 days. Relative to saline-treated controls, T3 rats had 80, 168, and 62% higher ATP production in soleus muscle, liver, and heart, respectively, as well as higher activities of citrate synthase (CS; 63, 90, 25%) and cytochrome c oxidase (COX; 119, 225, 52%) in the same tissues (all P , 0.01). In plantaris muscle of T3 rats, CS was only slightly higher (17%, P , 0.05) than in controls, and ATP production and COX were unaffected. mRNA levels of COX I and III were 33 and 47% higher in soleus of T3 rats (P , 0.01), but there were no differences in plantaris. In contrast, UCP2 and -3 mRNAs were 2.5to 14-fold higher, and protein levels were 3to 10-fold higher in both plantaris and soleus of the T3 group. We conclude that T3 increases oxidative enzymes and Mito ATP production and Mito-encoded transcripts in oxidative but not glycolytic rodent tissues. Despite large increases in UCP expression, ATP production was enhanced in oxidative tissues and maintained in glycolytic muscle of hyperthyroid rats.