Thyroid Hormone Action in Muscle Atrophy

Abstract

Skeletal muscle atrophy is a condition associated with various physiological and pathophysiological conditions, such as denervation, cachexia, and fasting. It is characterized by an altered protein turnover in which the rate of protein degradation exceeds the rate of protein synthesis, leading to substantial muscle mass loss and weakness. Muscle protein breakdown reflects the activation of multiple proteolytic mechanisms, including lysosomal degradation, apoptosis, and ubiquitin–proteasome. Thyroid hormone (TH) plays a key role in these conditions. Indeed, skeletal muscle is among the principal TH target tissue, where TH regulates proliferation, metabolism, differentiation, homeostasis, and growth. In physiological conditions, TH stimulates both protein synthesis and degradation, and an alteration in TH levels is often responsible for a specific myopathy. Intracellular TH concentrations are modulated in skeletal muscle by a family of enzymes named deiodinases; in particular, in muscle, deiodinases type 2 (D2) and type 3 (D3) are both present. D2 activates the prohormone T4 into the active form triiodothyronine (T3), whereas D3 inactivates both T4 and T3 by the removal of an inner ring iodine. Here we will review the present knowledge of TH action in skeletal muscle atrophy, in particular, on the molecular mechanisms presiding over the control of intracellular T3 concentration in wasting muscle conditions. Finally, we will discuss the possibility of exploiting the modulation of deiodinases as a possible therapeutic approach to treat muscle atrophy.

Associations between low muscle mass and clinical characteristics of health population in China

“…Secondly, some studies have indicated that subclinical hyperthyroidism-but not subclinical hypothyroidism-impacts muscle mass and strength in the older adult. For example, in an older adult Korean cohort, higher T4 levels have been associated with sarcopenia [ 20 ], aligning with our results. This could be due to the more stable nature of FT4.…”

Sex-Specific Differences in Lower Body Fat Distribution and Association with Physical Performance among Healthy Community-Dwelling Older Adults: A Pilot Study

“…Thyroid hormones are major determinants of muscle fiber composition. Individuals with hypothyroidism show characteristic myopathy, especially affecting type II muscle fibers [ 49 ]. Additionally, hypothyroid conditions are associated with the conversion of fast fiber types to slow fiber types [ 50 ].…”

Correlation analysis of FT3/FT4 and frailty in elderly patients with coronary heart disease

“…As an important TH plays signi cant role in muscle maintenance. T3 is an important factor regulating muscle function and is involved in muscle contraction, metabolism, myogenesis, and repair [20]. FT3 and FT4 are the main physiological components of TH, and most of FT3 is transformed by liver deiodinase and kidney FT4 [37].…”

“…FT3/FT4 ratio re ects the transformation process of FT4 to FT3 and can be used to evaluate the activity of deiodinase, which is considered a better representation of the thyroid function compared to FT3 and FT4. Some studies [16][17][18][19][20] have shown that a high level of the thyroid hormone (TH) is closely associated with dementia, diabetes, dyslipidemia, atherosclerotic C, osteoporosis and fracture, and muscle atrophy, leading to a decline in fat-related physiological functions and stress resistance. There is growing evidence that frailty is characterized by a "metabolic signature" [21], where TH is a key regulator of metabolism.…”