In mice, blocking a specific thyroid hormone receptor in muscle tissue leads to higher levels of sarcolipin mRNA in both slow- and fast-twitch muscle fibers, which may relate to how muscles generate...

Pro

Against

Mechanism

Synthesis from 1 study

How it works

When mice lose the TRα1 thyroid hormone receptor in their muscles, those muscles make more sarcolipin protein to generate heat by making the calcium pump waste energy instead of using it efficiently—this happens in both slow and fast muscle types, and helps keep body heat stable even though the...

Most probable mechanism

In Simple Terms

When the thyroid hormone receptor TRα1 is turned off in mouse muscles, the muscles respond by making more of a protein called sarcolipin, which causes the calcium pump (SERCA) to waste energy as heat instead of moving calcium efficiently; this happens in both slow-twitch and fast-twitch muscles, as shown by increased sarcolipin mRNA in multiple muscles, and helps maintain baseline heat production even though the normal thyroid hormone signal is lost (10.1096/fj.202001258RR).

Causal chain

Loss of thyroid hormone receptor alpha 1 (TRα1) in skeletal muscle disrupts normal transcriptional regulation of thermogenic genes, leading to reduced T3-mediated energy expenditure (10.1096/fj.202001258RR).

Verified by multiple studies

which leads to

In response to TRα1 loss, sarcolipin mRNA is transcriptionally upregulated in both slow-twitch (soleus) and fast-twitch (EDL, gastrocnemius, quadriceps) skeletal muscles under non-stimulated conditions (10.1096/fj.202001258RR).

Verified by multiple studies

which leads to

Increased sarcolipin protein binds to the SERCA pump, uncoupling ATP hydrolysis from calcium transport, which generates heat instead of enabling muscle contraction (10.1096/fj.202001258RR).

Supported by evidence

which leads to

This sarcolipin-mediated uncoupling partially compensates for impaired thyroid hormone-driven thermogenesis, as evidenced by elevated mitochondrial stress markers like GDF15 without a drop in resting energy expenditure (10.1096/fj.202001258RR).

Verified by multiple studies

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

Randomized Controlled Trial

Animal

2020 Nov

Contradicting (0)

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No contradicting evidence found

Gold Standard Evidence Needed

According to GRADE and EBM methodology, here is what ideal scientific evidence would look like to definitively prove or disprove this specific claim, ordered from strongest to weakest evidence.

Source Study

Thyroid hormone receptor α in skeletal muscle is essential for T3‐mediated increase in energy expenditure

Score: 13

DOI: 10.1096/fj.202001258RR

Similar Assertions

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, but the mice's ability to run and their motivation to exercise remain unchanged.

75%

In mice, a specific thyroid hormone receptor called TRα1 is not needed for thyroid hormone to affect energy production in fast-twitch muscle fibers, but it is required for thyroid hormone to increase energy production in slow-twitch muscle fibers.

74%

In mice, the thyroid hormone T3 raises body temperature even when the thyroid hormone receptor TRα1 is not functional in skeletal muscle, indicating that the temperature increase does not depend on this specific receptor in muscle tissue.

73%

In mice, the thyroid hormone T3 raises overall energy use by acting on a specific receptor, TRα1, in skeletal muscle. When this receptor is disabled in muscle tissue, the increase in energy use does not occur, even when T3 levels in the blood remain normal.

71%