Thyroid hormone activation by type2 deiodinase mediates exercise-induced peroxisome proliferator-activated receptor-gamma coactivator-1 alpha expression in skeletal muscle

Thyroid hormone activation by type2 deiodinase mediates exercise-induced peroxisome proliferator-activated receptor-gamma coactivator-1 alpha expression in skeletal muscle

Author Bocco, Barbara M. L. C. Autor UNIFESP Google Scholar
Louzada, Ruy A. N. Google Scholar
Silvestre, Diego H. S. Google Scholar
Santos, Maria C. S. Google Scholar
Anne-Palmer, Elena Google Scholar
Rangel, Igor F. Google Scholar
Abdalla, Sherine Google Scholar
Ferreira, Andrea C. Google Scholar
Ribeiro, Miriam O. Google Scholar
Gereben, Balazs Google Scholar
Carvalho, Denise P. Google Scholar
Bianco, Antonio C. Google Scholar
Werneck-de-Castro, Joao P. Google Scholar
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.
Keywords gating
Language English
Sponsor National Institute of Diabetes and Digestive and Kidney Diseases
Brazilian National Research Council (CNPq)
Carlos Chagas Filho Foundation for Research Support in Rio de Janeiro (FAPERJ)
American Thyroid Association (ATA)
Hungarian Research Fund (OTKA)
Coordination for the Improvement of Higher Education Personnel (CAPES)
Grant number NIH: R01 65055
ATA: M1301627
OTKA: K109415
Date 2016
Published in Journal Of Physiology-London. Hoboken, v. 594, n. 18, p. 5255-5269, 2016.
ISSN 0022-3751 (Sherpa/Romeo, impact factor)
Publisher Wiley-Blackwell
Extent 5255-5269
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000383571400023

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