Thyroid hormone activation by type 2 deiodinase mediates exercise-induced peroxisome proliferator-activated receptor-γ coactivator-1α expression in skeletal muscle

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dc.contributor.authorBocco B.M.L.C.
dc.contributor.authorLouzada R.A.N.
dc.contributor.authorSilvestre D.H.S.
dc.contributor.authorSantos M.C.S.
dc.contributor.authorAnne-Palmer E.
dc.contributor.authorRangel I.F.
dc.contributor.authorAbdalla S.
dc.contributor.authorFerreira A.C.
dc.contributor.authorRibeiro M.O.
dc.contributor.authorGereben B.
dc.contributor.authorCarvalho D.P.
dc.contributor.authorBianco A.C.
dc.contributor.authorWerneck-de-Castro J.P.
dc.date.accessioned2024-03-13T00:52:23Z
dc.date.available2024-03-13T00:52:23Z
dc.date.issued2016
dc.description.abstract© 2016 The Authors. The Journal of Physiology © 2016 The Physiological SocietyKey points: In skeletal muscle, physical exercise and thyroid hormone mediate the peroxisome proliferator-activated receptor-γ coactivator-1α (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 β-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-γ coactivator-1α (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 μm forskolin (2.2- vs. 1.3-fold; P < 0.05). Chronic exercise training (6 weeks) increased soleus muscle PGC-1a mRNA levels (∼25%) and the mitochondrial enzyme citrate synthase (∼20%). In contrast, PGC-1a expression did not change and citrate synthase decreased by ∼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 β-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.
dc.description.firstpage5255
dc.description.issuenumber18
dc.description.lastpage5269
dc.description.volume594
dc.identifier.doi10.1113/JP272440
dc.identifier.issn1469-7793
dc.identifier.urihttps://dspace.mackenzie.br/handle/10899/35926
dc.relation.ispartofJournal of Physiology
dc.rightsAcesso Aberto
dc.subject.otherlanguagegating
dc.subject.otherlanguageheterogeneity
dc.subject.otherlanguagephosphorylation
dc.subject.otherlanguagetrafficking
dc.titleThyroid hormone activation by type 2 deiodinase mediates exercise-induced peroxisome proliferator-activated receptor-γ coactivator-1α expression in skeletal muscle
dc.typeArtigo
local.scopus.citations37
local.scopus.eid2-s2.0-84982217643
local.scopus.subjectAnimals
local.scopus.subjectBlood Glucose
local.scopus.subjectCells, Cultured
local.scopus.subjectCitrate (si)-Synthase
local.scopus.subjectGene Expression
local.scopus.subjectIodide Peroxidase
local.scopus.subjectLactic Acid
local.scopus.subjectMale
local.scopus.subjectMice, Inbred C57BL
local.scopus.subjectMice, Knockout
local.scopus.subjectMuscle, Skeletal
local.scopus.subjectPeroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
local.scopus.subjectPhysical Conditioning, Animal
local.scopus.subjectRats, Wistar
local.scopus.subjectRNA, Messenger
local.scopus.subjectThyroxine
local.scopus.subjectTriiodothyronine
local.scopus.updated2024-05-01
local.scopus.urlhttps://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84982217643&origin=inward
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