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.

Thyroid Hormone Protects from Fasting-Induced Skeletal Muscle Atrophy by Promoting Metabolic Adaptation / Ucci, Sarassunta; Renzini, Alessandra; Russi, Valentina; Mangialardo, Claudia; Cammarata, Ilenia; Cavioli, Giorgia; Santaguida, Maria Giulia; Virili, Camilla; Centanni, Marco; Adamo, Sergio; Moresi, Viviana; Verga-Falzacappa, Cecilia. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1422-0067. - 20:22(2019). [10.3390/ijms20225754]

Thyroid Hormone Protects from Fasting-Induced Skeletal Muscle Atrophy by Promoting Metabolic Adaptation

Ucci, Sarassunta;Renzini, Alessandra;Mangialardo, Claudia;Cammarata, Ilenia;Cavioli, Giorgia;Santaguida, Maria Giulia;Virili, Camilla;Centanni, Marco;Adamo, Sergio;Moresi, Viviana
;
Verga-Falzacappa, Cecilia
2019

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.
2019
metabolic reprogramming; muscle atrophy; thyroid hormone
01 Pubblicazione su rivista::01a Articolo in rivista
Thyroid Hormone Protects from Fasting-Induced Skeletal Muscle Atrophy by Promoting Metabolic Adaptation / Ucci, Sarassunta; Renzini, Alessandra; Russi, Valentina; Mangialardo, Claudia; Cammarata, Ilenia; Cavioli, Giorgia; Santaguida, Maria Giulia; Virili, Camilla; Centanni, Marco; Adamo, Sergio; Moresi, Viviana; Verga-Falzacappa, Cecilia. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1422-0067. - 20:22(2019). [10.3390/ijms20225754]
File allegati a questo prodotto
File Dimensione Formato  
Ucci_Thyroid-hormone_2019.pdf

accesso aperto

Note: https://www.mdpi.com/1422-0067/20/22/5754
Tipologia: Versione editoriale (versione pubblicata con il layout dell'editore)
Licenza: Creative commons
Dimensione 1.59 MB
Formato Adobe PDF
1.59 MB Adobe PDF

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1330281
Citazioni
  • ???jsp.display-item.citation.pmc??? 3
  • Scopus 8
  • ???jsp.display-item.citation.isi??? 7
social impact