title: Leucine supplementation is anti-atrophic during paradoxical sleep deprivation in rats.
abstract: The purpose of this study was to identify sleep deprivation-induced atrophy and the muscle-specific fiber types affected and to determine the effects of leucine supplementation on atrophy and pertinent portions of the pathways of muscle protein synthesis and degradation in rats. A total of 46 Wistar rats were distributed in four groups: control (CTL), leucine supplementation (LEU), sleep deprivation (SD), and leucine supplementation + sleep deprivation (LEU + SD). Leucine supplementation was by gavage (1.35 g/kg/daily), and the animals were subjected to SD for 96 h. Testosterone and corticosterone concentrations, along with proteins involved in protein synthesis and degradation and proteasome activity levels, were measured in the gastrocnemius (GA) muscle. Myosin ATPase staining was used to evaluate the different muscle fibers. After sleep deprivation, GA muscle and body masses decreased in the SD group compared to the CTL, LEU, and LEU + SD groups. There was no difference between groups in type I fiber cross-sectional area (CSA). The CSAs for type IIa fibers were lower in the SD and LEU + SD groups vs. the CTL and LEU groups, while the IIb fiber CSA was lower in the SD group vs. the CSAs in all other groups. The phospho (p)-Akt levels were lower in the SD and LEU + SD groups vs. the CTL and LEU groups. The p-mTORC1 levels were higher in the LEU, SD, and LEU + SD groups vs. the CTL group. The p-p70S6k levels were higher in the LEU and LEU + SD groups; the 4E-BP1 levels were higher in the SD and LEU + SD groups compared to those in the CTL and LEU groups, and the p-4E-BP1 levels were higher in the LEU and SD groups compared to those in the CTL group and even higher in the LEU + SD group compared to those in the LEU and SD groups. Ubiquitinated proteins, LC3, and p62/SQSTM, and proteasome activity levels were higher in the SD and LEU + SD groups vs. the LEU and CTL groups. Sleep deprivation led to the atrophy of IIa and IIb muscle fibers; however, leucine supplementation prevented muscle loss and type IIb fiber atrophy.
authors.affiliation: Departamento de Psicobiologia, Universidade Federal de São Paulo, São Paulo, SP, Brazil.|Laboratório Interdisciplinar em Fisiologia e Exercício (LAIFE), São Paulo, SP, Brazil.
authors.forename: Helton
authors.initials: H
authors.lastname: de Sá Souza
authors.affiliation: Departamento de Psicobiologia, Universidade Federal de São Paulo, São Paulo, SP, Brazil. hanna.karen@unifesp.br.|Departamento de Biociências, Universidade Federal de São Paulo, Campus Baixada Santista, Rua: Silva Jardim, 136, Térreo-Vila Mathias, São Paulo, SP, CEP: 11015-020, Brazil. hanna.karen@unifesp.br.|Laboratório Interdisciplinar em Fisiologia e Exercício (LAIFE), São Paulo, SP, Brazil. hanna.karen@unifesp.br.
authors.forename: Hanna Karen Moreira
authors.initials: HKM
authors.lastname: Antunes
authors.affiliation: Departamento de Psicobiologia, Universidade Federal de São Paulo, São Paulo, SP, Brazil.|Laboratório Interdisciplinar em Fisiologia e Exercício (LAIFE), São Paulo, SP, Brazil.
authors.forename: Murilo
authors.initials: M
authors.lastname: Dáttilo
authors.affiliation: Departamento de Bioquímica, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
authors.forename: Kil Sun
authors.initials: KS
authors.lastname: Lee
authors.affiliation: Departamento de Psicobiologia, Universidade Federal de São Paulo, São Paulo, SP, Brazil.|Laboratório Interdisciplinar em Fisiologia e Exercício (LAIFE), São Paulo, SP, Brazil.
authors.forename: Marcos
authors.initials: M
authors.lastname: Mônico-Neto
authors.affiliation: Departamento de Psicobiologia, Universidade Federal de São Paulo, São Paulo, SP, Brazil.|Laboratório Interdisciplinar em Fisiologia e Exercício (LAIFE), São Paulo, SP, Brazil.
authors.forename: Sara Quaglia
authors.initials: SQ
authors.lastname: de Campos Giampa
authors.affiliation: Department of Kinesiology, McMaster University, Hamilton, ON, Canada.
authors.forename: Stuart M
authors.initials: SM
authors.lastname: Phillips
authors.affiliation: Departamento de Psicobiologia, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
authors.forename: Sergio
authors.initials: S
authors.lastname: Tufik
authors.affiliation: Escola de Educação Física, Fisioterapia e Terapia Ocupacional, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Marco Túlio
authors.initials: MT
authors.lastname: de Mello
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D003345:Corticosterone / Q000378:metabolism; D019587:Dietary Supplements; D005786:Gene Expression Regulation; D047908:Intracellular Signaling Peptides and Proteins; D007930:Leucine / Q000008:administration & dosage*; D008297:Male; D000076222:Mechanistic Target of Rapamycin Complex 1; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism; D018485:Muscle Fibers, Skeletal / Q000145:classification / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009133:Muscular Atrophy / Q000150:complications / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D009218:Myosins / Q000235:genetics / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000235:genetics / Q000378:metabolism; D000071456:Sequestosome-1 Protein / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D012892:Sleep Deprivation / Q000150:complications / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D013739:Testosterone / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D003345:Corticosterone; D047908:Intracellular Signaling Peptides and Proteins; D007930:Leucine; D000076222:Mechanistic Target of Rapamycin Complex 1; D008869:Microtubule-Associated Proteins; D046912:Multiprotein Complexes; D009218:Myosins; D010750:Phosphoproteins; D046988:Proteasome Endopeptidase Complex; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D000071456:Sequestosome-1 Protein; D058570:TOR Serine-Threonine Kinases; D013739:Testosterone; C499526:Eif4ebp1 protein, rat; C526109:Anxa3 protein, rat; C491079:Sqstm1 protein, rat
keywords: Protein degradation; Protein synthesis; Skeletal muscle; mTORC1