Thyroid Hormone Protects from Fasting-Induced Skeletal Muscle Atrophy by Promoting Metabolic Adaptation
Sarassunta Ucci1, Alessandra Renzini2, Valentina Russi1
1Pasteur Institute, 00161 Rome, Italy.
Abstract:
Thyroid hormones regulate a wide range of cellular responses, via non-genomic and genomic actions, depending on cell-specific thyroid hormone transporters, co-repressors, or co-activators. Skeletal muscle has been identified as a direct target of thyroid hormone T3, where it regulates stem cell proliferation and differentiation, as well as myofiber metabolism. However, the effects of T3 in muscle-wasting conditions have not been yet addressed. Being T3 primarily responsible for the regulation of metabolism, we challenged mice with fasting and found that T3 counteracted starvation-induced muscle atrophy. Interestingly, T3 did not prevent the activation of the main catabolic pathways, i.e., the ubiquitin-proteasome or the autophagy-lysosomal systems, nor did it stimulate de novo muscle synthesis in starved muscles. Transcriptome analyses revealed that T3 mainly affected the metabolic processes in starved muscle. Further analyses of myofiber metabolism revealed that T3 prevented the starvation-mediated metabolic shift, thus preserving skeletal muscle mass. Our study elucidated new T3 functions in regulating skeletal muscle homeostasis and metabolism in pathological conditions, opening to new potential therapeutic approaches for the treatment of skeletal muscle atrophy.
Insights
Thyroid hormone T3 counteracts muscle atrophy during starvation by preserving myofiber metabolism, not by blocking catabolic pathways or stimulating muscle synthesis. This research reveals new T3 functions for skeletal muscle homeostasis.
Area of Science:
- Endocrinology
- Muscle Physiology
- Molecular Biology
Background:
- Thyroid hormones, particularly T3, regulate cellular functions through genomic and non-genomic pathways.
- Skeletal muscle is a direct target of T3, influencing stem cell activity and myofiber metabolism.
- The role of T3 in muscle-wasting conditions like starvation remains largely unexplored.
Purpose of the Study:
- To investigate the effects of thyroid hormone T3 on skeletal muscle during starvation-induced atrophy.
- To elucidate the mechanisms by which T3 influences muscle metabolism and homeostasis under catabolic stress.
Main Methods:
- Mice were subjected to fasting to induce muscle atrophy.
- Transcriptome analysis was performed on starved muscles treated with T3.
- Myofiber metabolism was analyzed to assess the impact of T3 on metabolic shifts.
Main Results:
- Thyroid hormone T3 counteracted starvation-induced muscle atrophy in mice.
- T3 did not inhibit major catabolic pathways (ubiquitin-proteasome, autophagy-lysosomal).
- T3 preserved skeletal muscle mass by preventing a starvation-mediated metabolic shift in myofibers.
Conclusions:
- Thyroid hormone T3 plays a crucial role in maintaining skeletal muscle homeostasis during fasting.
- T3's protective effect is mediated by regulating metabolic processes rather than inhibiting catabolism.
- These findings suggest potential therapeutic strategies targeting T3 for muscle atrophy treatment.
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