Abstract
This study investigated the effect of leucine supplementation on the skeletal muscle regenerative process, focusing on the remodeling of connective tissue of the fast twitch muscle tibialis anterior (TA). Young male Wistar rats were supplemented with leucine (1.35 g/kg per day); then, TA muscles from the left hind limb were cryolesioned and examined after 10 days. Although leucine supplementation induced increased protein synthesis, it was not sufficient to promote an increase in the cross-sectional area (CSA) of regenerating myofibers (p > 0.05) from TA muscles. However, leucine supplementation reduced the amount of collagen and the activation of phosphorylated transforming growth factor-β receptor type I (TβR-I) and Smad2/3 in regenerating muscles (p < 0.05). Leucine also reduced neonatal myosin heavy chain (MyHC-n) (p < 0.05), increased adult MyHC-II expression (p < 0.05) and prevented the decrease in maximum tetanic strength in regenerating TA muscles (p < 0.05). Our results suggest that leucine supplementation accelerates connective tissue repair and consequent function of regenerating TA through the attenuation of TβR-I and Smad2/3 activation. Therefore, future studies are warranted to investigate leucine supplementation as a nutritional strategy to prevent or attenuate muscle fibrosis in patients with several muscle diseases.
Highlights
Adult skeletal myofibers have a remarkable capacity of regeneration after muscle damage [1].The muscle regenerative process includes migration of immune cells, such as neutrophils and macrophages, to the site of injury, the proliferation and differentiation of satellite cells and the remodelling of connective tissue and angiogenesis, resulting in the functional recovery of damaged muscles [2,3]
C, control muscles; leucine supplemented-only muscles (Leu), muscles after 13 days of leucine supplementation; Cryo, muscles analyzed on Day 10 post-cryolesion; Cryo + Leu, leucine supplemented group analyzed on Day 10 post-cryolesion
C, control muscles; Cryo, muscles analyzed on Day 10 post-cryolesion; Leu, muscles after 13 days of leucine supplementation; Cryo + Leu, leucine supplemented group analyzed on Day 10 post-cryolesion
Summary
Adult skeletal myofibers have a remarkable capacity of regeneration after muscle damage [1]. The muscle regenerative process includes migration of immune cells, such as neutrophils and macrophages, to the site of injury, the proliferation and differentiation of satellite cells and the remodelling of connective tissue and angiogenesis, resulting in the functional recovery of damaged muscles [2,3]. As previously established by us and others, the phosphoinositide 3-kinase (PI3K)/Akt/mechanistic target of the rapamycin pathway and the ubiquitin proteasome system play significant roles in skeletal muscle mass recovery after injury [5,6,7,8,9,10]. The growth of regenerating myofibers is dependent on various processes, such as satellite cell proliferation, myotube formation, angiogenesis and the re-establishment of neuromuscular and connective tissue. Regenerated myofibers can be recognized by the presence of centrally located nuclei, which are a hallmark of muscle regeneration [11]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
