When thyroid hormone receptor alpha 1 is removed from the skeletal muscle of mice, the slow-twitch muscle fibers in the soleus muscle become more dominated by type I fibers and fewer type IIA fibers,...
Mechanism
Synthesis from 1 study
When the TRα1 receptor is removed from mouse leg muscles, the muscle fibers switch from a faster type (IIA) to a slower, more efficient type (I) because the genes controlling this switch are no longer turned off — this change happens without making the mice run more or less, as shown in the study...
Most probable mechanism
When the thyroid hormone receptor TRα1 is turned off in mouse leg muscles, the slow-twitch muscle fibers change from a faster type (IIA) to a slower, more efficient type (I) because the genes that control fiber type are no longer suppressed — this happens without changing how much the mice run or how motivated they are to exercise, as shown in the study with DOI 10.1096/fj.202001258RR.
Loss of thyroid hormone receptor alpha 1 (TRα1) in skeletal muscle disrupts transcriptional repression of slow-fiber genes and activation of fast-fiber genes in the soleus muscle, leading to increased expression of MyHC-I and decreased expression of MyHC-IIA.
This transcriptional shift results in a measurable increase in the proportion of type I (oxidative) fibers and a decrease in type IIA fibers in the soleus muscle, confirmed by immunofluorescence staining.
The fiber-type shift occurs independently of changes in mitochondrial capacity, energy expenditure, or exercise behavior, as running capacity and voluntary motivation remain unchanged despite altered gene expression and fiber composition.
Less supported by current evidence, but not ruled out
When TRα1 is lost, muscle cells increase sarcolipin to generate heat by wasting ATP, but this does not cause the shift from type IIA to type I fibers — it only creates metabolic stress without changing muscle performance or fiber composition.
Loss of TRα1 leads to a >5-fold increase in sarcolipin expression in soleus and other muscles, independent of thyroid hormone stimulation.
Increased sarcolipin uncouples SERCA-mediated ATP hydrolysis, increasing mitochondrial stress and elevating circulating GDF15, a marker of cellular stress.
This compensatory thermogenic mechanism does not alter fiber-type composition or exercise capacity, indicating it is a parallel metabolic response unrelated to the MyHC isoform switch.
Evidence from Studies
Supporting (1)
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Thyroid hormone receptor α in skeletal muscle is essential for T3‐mediated increase in energy expenditure
Contradicting (0)
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