Endocrine Abstracts

Purpose: Skeletal muscle has been recognized as a thyroid hormones (THs) target for contractile function, regeneration, metabolism and glucose disposal. Despite a role in regulating muscle development has been described, little is known about the role of THs in regulating muscle homeostasis in a pathological state such as food deprivation induced atrophy. The purpose of this study is to evaluate whether thyroid hormones may hamper the fasting induced skeletal muscle atrophy and to investigate the mechanisms involved.

Methods: Preliminary data on C2C12 myotubes have suggested that T3 could counteract the starvation induced atrophy in vitro. Based on these results, BALB/C male mice (8–10 weeks) were used for in vivo experiments. Animals were food-deprived (STV) for 24 and 48 hours to induce muscle atrophy and daily injected intraperitoneally with T3 (100 ug/kgBW) or vehicle (NaCl 0,95%) as controls. Tibialis anteriors were taken at the end of the experiments. Morphological analyses were performed on hematoxylin/eosin stained sections. ATG7-Mrna was evaluated by Sybr-Green qRT-PCR and LC3II/Lc3I was evaluated by western blot.

Results and conclusions: As a sign of skeletal muscle atrophy, the STV group showed a significant (P<0.001) reduction in the Cross-Sectional-Area of the myofibers, compared to the control group; on the contrary the T3 treated group (STVT3) ensures the maintenance of the fiber size. Protein degradation in skeletal muscle cells is mediated by the autophagic/lysosomal pathway. The core autophagic machinery is composed of ATG (autophagy-related) proteins. One ATG family member, Atg7, activates enzyme facilitating microtubule-associated protein-light-chain3 (LC3)-phosphatidylethanolamine conjugation. The presence of T3 was able to significantly reduce ATG7 mRNA expression, moreover the hormone significantly reduces LC3II/LC3I protein expression, when compared to STV mice (P<0,05). On the whole our results suggest that T3 treatment can reduce fasting induced skeletal muscle atrophy by counteracting the autophagic process.