| First Author | Bocco BM | Year | 2016 |
| Journal | J Physiol | Volume | 594 |
| Issue | 18 | Pages | 5255-69 |
| PubMed ID | 27302464 | Mgi Jnum | J:337884 |
| Mgi Id | MGI:6882886 | Doi | 10.1113/JP272440 |
| Citation | Bocco BM, et al. (2016) Thyroid hormone activation by type 2 deiodinase mediates exercise-induced peroxisome proliferator-activated receptor-gamma coactivator-1alpha expression in skeletal muscle. J Physiol 594(18):5255-69 |
| abstractText | KEY POINTS: In skeletal muscle, physical exercise and thyroid hormone mediate the peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1a) expression that is crucial to skeletal muscle mitochondrial function. The expression of type 2 deiodinase (D2), which activates thyroid hormone in skeletal muscle is upregulated by acute treadmill exercise through a beta-adrenergic receptor-dependent mechanism. Pharmacological block of D2 or disruption of the Dio2 gene in skeletal muscle fibres impaired acute exercise-induced PGC-1a expression. Dio2 disruption also impaired muscle PGC-1a expression and mitochondrial citrate synthase activity in chronically exercised mice. ABSTRACT: Thyroid hormone promotes expression of peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1a), which mediates mitochondrial biogenesis and oxidative capacity in skeletal muscle (SKM). Skeletal myocytes express the type 2 deiodinase (D2), which generates 3,5,3'-triiodothyronine (T3 ), the active thyroid hormone. To test whether D2-generated T3 plays a role in exercise-induced PGC-1a expression, male rats and mice with SKM-specific Dio2 inactivation (SKM-D2KO or MYF5-D2KO) were studied. An acute treadmill exercise session (20 min at 70-75% of maximal aerobic capacity) increased D2 expression/activity (1.5- to 2.7-fold) as well as PGC-1a mRNA levels (1.5- to 5-fold) in rat soleus muscle and white gastrocnemius muscle and in mouse soleus muscle, which was prevented by pretreatment with 1 mg (100 g body weight)(-1) propranolol or 6 mg (100 g body weight)(-1) iopanoic acid (5.9- vs. 2.8-fold; P < 0.05), which blocks D2 activity . In the SKM-D2KO mice, acute treadmill exercise failed to induce PGC-1a fully in soleus muscle (1.9- vs. 2.8-fold; P < 0.05), and in primary SKM-D2KO myocytes there was only a limited PGC-1a response to 1 mum forskolin (2.2- vs. 1.3-fold; P < 0.05). Chronic exercise training (6 weeks) increased soleus muscle PGC-1a mRNA levels ( approximately 25%) and the mitochondrial enzyme citrate synthase ( approximately 20%). In contrast, PGC-1a expression did not change and citrate synthase decreased by approximately 30% in SKM-D2KO mice. The soleus muscle PGC-1a response to chronic exercise was also blunted in MYF5-D2KO mice. In conclusion, acute treadmill exercise increases SKM D2 expression through a beta-adrenergic receptor-dependent mechanism. The accelerated conversion of T4 to T3 within myocytes mediates part of the PGC-1a induction by treadmill exercise and its downstream effects on mitochondrial function. |
