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 microg/kg/day). Oxidative capacity, regulation of mitochondrial respiration by substrates and phosphate acceptors, and transcription factors were studied. In soleus, T3 treatment increased maximal oxygen consumption (Vmax) and the activities of citrate synthase (CS) and cytochrome oxidase (COX) by 100%, 45%, and 71%, respectively (P < 0.001), whereas in plantaris only Vmax 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-1alpha, 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, TRalpha mRNA level decreased further after T3 treatment. These results demonstrate that TH has a major effect on 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-1alpha transcription factor.
Bahi
L
L
INSERM U-446, Laboratoire de Cardiologie Cellulaire et Moléculaire, Châtenay-Malabry Cedex, France.
Garnier
A
A
Fortin
D
D
Serrurier
B
B
Veksler
V
V
Bigard
A X
AX
Ventura-Clapier
R
R
D000244:Adenosine Diphosphate / Q000378:metabolism; D000818:Animals; D019069:Cell Respiration / Q000187:drug effects / Q000502:physiology; D002950:Citrate (si)-Synthase / Q000187:drug effects / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000187:drug effects / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects* / Q000502:physiology*; D007770:L-Lactate Dehydrogenase / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D018656:Muscle Fibers, Fast-Twitch / Q000187:drug effects / Q000378:metabolism*; D018657:Muscle Fibers, Slow-Twitch / Q000187:drug effects / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D009924:Organ Culture Techniques; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D037021:Thyroid Hormone Receptors alpha / Q000235:genetics; D013963:Thyroid Hormones / Q000494:pharmacology*; D014157:Transcription Factors / Q000235:genetics; D014284:Triiodothyronine / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D037021:Thyroid Hormone Receptors alpha; D013963:Thyroid Hormones; D014157:Transcription Factors; D014284:Triiodothyronine; D000244:Adenosine Diphosphate; D007770:L-Lactate Dehydrogenase; D003576:Electron Transport Complex IV; D002950:Citrate (si)-Synthase