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

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dc.contributor.author Bocco, Barbara M. L. C. [UNIFESP]
dc.contributor.author Louzada, Ruy A. N.
dc.contributor.author Silvestre, Diego H. S.
dc.contributor.author Santos, Maria C. S.
dc.contributor.author Anne-Palmer, Elena
dc.contributor.author Rangel, Igor F.
dc.contributor.author Abdalla, Sherine
dc.contributor.author Ferreira, Andrea C.
dc.contributor.author Ribeiro, Miriam O.
dc.contributor.author Gereben, Balazs
dc.contributor.author Carvalho, Denise P.
dc.contributor.author Bianco, Antonio C.
dc.contributor.author Werneck-de-Castro, Joao P.
dc.date.accessioned 2019-07-22T15:46:31Z
dc.date.available 2019-07-22T15:46:31Z
dc.date.issued 2016
dc.identifier http://dx.doi.org/10.1113/JP272440
dc.identifier.citation Journal Of Physiology-London. Hoboken, v. 594, n. 18, p. 5255-5269, 2016.
dc.identifier.issn 0022-3751
dc.identifier.uri http://repositorio.unifesp.br/handle/11600/50963
dc.description.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 en
dc.description.abstract 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 en
dc.description.abstract 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 en
dc.description.abstract 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. en
dc.description.sponsorship National Institute of Diabetes and Digestive and Kidney Diseases
dc.description.sponsorship Brazilian National Research Council (CNPq)
dc.description.sponsorship Carlos Chagas Filho Foundation for Research Support in Rio de Janeiro (FAPERJ)
dc.description.sponsorship American Thyroid Association (ATA)
dc.description.sponsorship Hungarian Research Fund (OTKA)
dc.description.sponsorship Coordination for the Improvement of Higher Education Personnel (CAPES)
dc.format.extent 5255-5269
dc.language.iso eng
dc.publisher Wiley-Blackwell
dc.rights Acesso aberto
dc.subject gating en
dc.subject heterogeneity en
dc.subject phosphorylation en
dc.subject trafficking en
dc.title Thyroid hormone activation by type2 deiodinase mediates exercise-induced peroxisome proliferator-activated receptor-gamma coactivator-1 alpha expression in skeletal muscle en
dc.type Artigo
dc.description.affiliation Rush Univ, Med Ctr, Div Endocrinol & Metab, Chicago, IL 60612 USA
dc.description.affiliation Univ Fed Sao Paulo, Dept Translat Med, Sao Paulo, Brazil
dc.description.affiliation Univ Fed Rio de Janeiro, Inst Biophys Carlos Chagas Filho, BR-21941 Rio De Janeiro, Brazil
dc.description.affiliation Univ Fed Rio de Janeiro, Sch Phys Educ & Sports, BR-21941 Rio De Janeiro, Brazil
dc.description.affiliation Univ Miami, Miller Sch Med, Div Endocrinol Diabet & Metab, Miami, FL 33136 USA
dc.description.affiliation Univ Prebiteriana Mackenzie, Dev Disorders Program, Ctr Biol & Hlth Sci, Sao Paulo, Brazil
dc.description.affiliation Hungarian Acad Sci, Dept Endocrine Neurobiol, Inst Expt Med, Budapest, Hungary
dc.description.affiliationUnifesp Univ Fed Sao Paulo, Dept Translat Med, Sao Paulo, Brazil
dc.description.sponsorshipID NIH: R01 65055
dc.description.sponsorshipID ATA: M1301627
dc.description.sponsorshipID OTKA: K109415
dc.identifier.file WOS000383571400023.pdf
dc.identifier.doi 10.1113/JP272440
dc.description.source Web of Science
dc.identifier.wos WOS:000383571400023



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