Thyroid hormone activation by type 2 deiodinase mediates exercise-induced peroxisome proliferator-activated receptor-γ coactivator-1α expression in skeletal muscle.
Level 5 - mechanism / opinion, no new human data
Animal and in vitro mechanistic laboratory study without human data.
PubMed 27302464 · doi:10.1113/JP272440
What was done
Male rats and skeletal muscle-specific Dio2 knockout mice (SKM-D2KO and MYF5-D2KO) were subjected to acute treadmill running (20 min at 70–75% maximal aerobic capacity) with or without propranolol (1 mg/100 g body weight) or the D2 inhibitor iopanoic acid (6 mg/100 g body weight). Other cohorts underwent chronic treadmill training for 6 weeks. Primary SKM-D2KO myocytes were also stimulated with 1 μm forskolin. Outcomes included muscle D2 activity/expression, PGC-1α mRNA levels in soleus and white gastrocnemius, and citrate synthase activity.
What was found
Acute exercise increased muscle D2 expression/activity 1.5- to 2.7-fold and PGC-1α mRNA 1.5- to 5-fold across rat muscles and mouse soleus; propranolol prevented D2 upregulation, and iopanoic acid blunted PGC-1α induction (2.8-fold vs. 5.9-fold, P < 0.05). In SKM-D2KO mice, acute exercise-induced soleus PGC-1α expression was impaired (1.9-fold vs. 2.8-fold, P < 0.05), and in vitro myocyte PGC-1α induction by forskolin was reduced (1.3-fold vs. 2.2-fold, P < 0.05). Following 6 weeks of chronic exercise, control mice showed increases in soleus PGC-1α mRNA (~25%) and citrate synthase activity (~20%), whereas SKM-D2KO mice showed no change in PGC-1α and a ~30% decrease in citrate synthase.
Why it matters
These findings establish that local intracellular conversion of T4 to T3 by type 2 deiodinase is a necessary β-adrenergic-dependent step for exercise-induced PGC-1α expression and downstream mitochondrial adaptations in skeletal muscle.
Limits
The study is restricted to rodent models and primary cell cultures with no human validation. Total animal counts, specific group sample sizes, and variance estimates are not reported in the abstract.
Cited by
- supports Active skeletal muscle is a major site for the conversion of T4 into active T3.