title: Leucine supplementation accelerates connective tissue repair of injured tibialis anterior muscle.
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.
authors.affiliation: Department of Anatomy, Institute of Biomedical Sciences, University of Sao Paulo, Prof. Lineu Prestes Av. 2415, Sao Paulo, SP 05508-000, Brazil. pereiramg@gmail.com.
authors.forename: Marcelo G
authors.initials: MG
authors.lastname: Pereira
authors.affiliation: Department of Anatomy, Institute of Biomedical Sciences, University of Sao Paulo, Prof. Lineu Prestes Av. 2415, Sao Paulo, SP 05508-000, Brazil. me_tomaz@hotmail.com.
authors.forename: Meiricris T
authors.initials: MT
authors.lastname: Silva
authors.affiliation: Department of Anatomy, Institute of Biomedical Sciences, University of Sao Paulo, Prof. Lineu Prestes Av. 2415, Sao Paulo, SP 05508-000, Brazil. eduardo.carlassara@usp.br.
authors.forename: Eduardo O C
authors.initials: EO
authors.lastname: Carlassara
authors.affiliation: Department of Physiology and Biochemistry/Immunology, School of Medicine, University of Sao Paulo, Bandeirantes Av. 3900, Ribeirao Preto, SP 14049-900, Brazil. dawitapg@yahoo.com.br.
authors.forename: Dawit A
authors.initials: DA
authors.lastname: Gonçalves
authors.affiliation: Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of Sao Paulo, Prof. Lineu Prestes Av. 1524, Sao Paulo, SP 05508-000, Brazil. pauloabrahamsohn@gmail.com.
authors.forename: Paulo A
authors.initials: PA
authors.lastname: Abrahamsohn
authors.affiliation: Department of Physiology and Biochemistry/Immunology, School of Medicine, University of Sao Paulo, Bandeirantes Av. 3900, Ribeirao Preto, SP 14049-900, Brazil. idckette@fmrp.usp.br.
authors.forename: Isis C
authors.initials: IC
authors.lastname: Kettelhut
authors.affiliation: Department of Anatomy, Institute of Biomedical Sciences, University of Sao Paulo, Prof. Lineu Prestes Av. 2415, Sao Paulo, SP 05508-000, Brazil. moriscot@usp.br.
authors.forename: Anselmo S
authors.initials: AS
authors.lastname: Moriscot
authors.affiliation: School of Arts, Sciences and Humanities, University of Sao Paulo, Arlindo Bettio Av. 1000, Sao Paulo, SP 03828-000, Brazil. aoki.ms@usp.br.
authors.forename: Marcelo S
authors.initials: MS
authors.lastname: Aoki
authors.affiliation: Department of Anatomy, Institute of Biomedical Sciences, University of Sao Paulo, Prof. Lineu Prestes Av. 2415, Sao Paulo, SP 05508-000, Brazil. elenm@usp.br.
authors.forename: Elen H
authors.initials: EH
authors.lastname: Miyabara
mesh_terms: D000818:Animals; D003094:Collagen / Q000187:drug effects; D003238:Connective Tissue / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D019587:Dietary Supplements; D007930:Leucine / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D018482:Muscle, Skeletal / Q000293:injuries* / Q000378:metabolism; D009210:Myofibrils / Q000187:drug effects; D018995:Myosin Heavy Chains / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D012038:Regeneration / Q000187:drug effects; D051899:Smad2 Protein / Q000378:metabolism; D051900:Smad3 Protein / Q000378:metabolism; D013035:Spasm / Q000178:diet therapy; D013977:Tibia
chemical_list: D018125:Receptors, Transforming Growth Factor beta; D051899:Smad2 Protein; C497784:Smad2 protein, rat; D051900:Smad3 Protein; C497787:Smad3 protein, rat; D003094:Collagen; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625843:Tgfbr1 protein, rat; D018995:Myosin Heavy Chains; D007930:Leucine