Differential effects of thyroid hormones on energy metabolism of rat slow- and fast-twitch muscles

Thyroid hormone (TH) is an important regulator of mitochondrial content and activity. As mitochondrial content and properties differ depending on muscle-type, we compared mitochondrial regulation and biogenesis by T3 in slow-twitch oxidative (soleus) and fast-twitch mixed muscle (plantaris). Male Wistar rats were treated for 21 to 27 days with T3 (200 mu g/kg/day). Oxidative capacity, regulation of mitochondrial respiration by substrates and phosphate acceptors, and transcription factors were Studied. III soleus, T3 treatment increased maximal oxygen consumption (V-max) and the activities of citrate synthase (CS) and cytochrome oxidase (COX) by 100%, 45%, and 71%, respectively (P < 0.001), whereas in plantaris only V-max increased, by 39% (P < 0.01). ADP-independent respiration rate was increased in soleus Muscle by 216% Suggesting mitochondrial uncoupling. Mitochondrial substrate utilization in soleus was also influenced by T3, as were mitochondrial enzymes. Lactate dehydrogenase (LDH) activity was elevated in soleus and plantaris by 63% and 11%, respectively (P < 0.01), and soleus creatine kinase was increased by 48% (P < 0.001). T3 increased the mRNA content of the transcriptional co-activator of mitochondrial genes, PGC-1 alpha, and the I and IV COX subunits in soleus. The muscle specific response to thyroid hormones Could be explained by a lower content of TH receptors in plantaris than soleus. Moreover, TR alpha mRNA level decreased further after T3 treatment. These results demonstrate that TH has a major effect oil mitochondrial content, regulation and coupling in slow oxidative muscle, but to a lesser extent in fast muscle, due to the high expression of TH receptors and PGC-1 alpha transcription factor. (c) 2004 Wiley-Liss, Inc.