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|Title:||Thyroid hormone activation by type2 deiodinase mediates exercise-induced peroxisome proliferator-activated receptor-gamma coactivator-1 alpha expression in skeletal muscle|
|Authors:||Bocco, Barbara M. L. C. [UNIFESP]|
Louzada, Ruy A. N.
Silvestre, Diego H. S.
Santos, Maria C. S.
Rangel, Igor F.
Ferreira, Andrea C.
Ribeiro, Miriam O.
Carvalho, Denise P.
Bianco, Antonio C.
Werneck-de-Castro, Joao P.
|Citation:||Journal Of Physiology-London. Hoboken, v. 594, n. 18, p. 5255-5269, 2016.|
|Abstract:||Key points In skeletal muscle, physical exercise and thyroid hormone mediate the peroxisome proliferator-activated receptor- coactivator-1 (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 -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. AbstractThyroid hormone promotes expression of peroxisome proliferator-activated receptor- coactivator-1 (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 (T-3), the active thyroid hormone. To test whether D2-generated T-3 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 (20min 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 1mg(100g body weight)(-1) propranolol or 6mg(100g 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 1m forskolin (2.2- vs. 1.3-fold
P<0.05). Chronic exercise training (6weeks) increased soleus muscle PGC-1a mRNA levels (approximate to 25%) and the mitochondrial enzyme citrate synthase (approximate to 20%). In contrast, PGC-1a expression did not change and citrate synthase decreased by approximate to 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 -adrenergic receptor-dependent mechanism. The accelerated conversion of T-4 to T-3 within myocytes mediates part of the PGC-1a induction by treadmill exercise and its downstream effects on mitochondrial function.
|Appears in Collections:||Artigo|
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