title: Impact of leucine supplementation on exercise training induced anti-cardiac remodeling effect in heart failure mice.
abstract: Leucine supplementation potentiates the effects of aerobic exercise training (AET) on skeletal muscle; however, its potential effects associated with AET on cardiac muscle have not been clarified yet. We tested whether leucine supplementation would potentiate the anti-cardiac remodeling effect of AET in a genetic model of sympathetic hyperactivity-induced heart failure in mice (α2A/α2CARKO). Mice were assigned to five groups: wild type mice treated with placebo and sedentary (WT, n = 11), α2A/α2CARKO treated with placebo and sedentary (KO, n = 9), α2A/α2CARKO treated with leucine and sedentary (KOL, n = 11), α2A/α2CARKO treated with placebo and AET (KOT, n = 12) or α2A/α2CARKO treated with leucine and AET (KOLT, n = 12). AET consisted of four weeks on a treadmill with 60 min sessions (six days/week, 60% of maximal speed) and administration by gavage of leucine (1.35 g/kg/day) or placebo (distilled water). The AET significantly improved exercise capacity, fractional shortening and re-established cardiomyocytes' diameter and collagen fraction in KOT. Additionally, AET significantly prevented the proteasome hyperactivity, increased misfolded proteins and HSP27 expression. Isolated leucine supplementation displayed no effect on cardiac function and structure (KOL), however, when associated with AET (KOLT), it increased exercise tolerance to a higher degree than isolated AET (KOT) despite no additional effects on AET induced anti-cardiac remodeling. Our results provide evidence for the modest impact of leucine supplementation on cardiac structure and function in exercised heart failure mice. Leucine supplementation potentiated AET effects on exercise tolerance, which might be related to its recognized impact on skeletal muscle.
authors.affiliation: Biosciences Department, Federal University of São Paulo, Santos, 11015-020, Brazil. wmaxnutri@gmail.com.|School of Physical Education and Sport, University of São Paulo, São Paulo, 05508-900, Brazil. wmaxnutri@gmail.com.
authors.forename: Wilson Max Almeida Monteiro
authors.initials: WM
authors.lastname: de Moraes
authors.affiliation: School of Physical Education and Sport, University of São Paulo, São Paulo, 05508-900, Brazil. thamelara@hotmail.com.
authors.forename: Thaís Plasti
authors.initials: TP
authors.lastname: Melara
authors.affiliation: Post-graduation Program in Medicine, Nove de Julho University (UNINOVE), São Paulo, 01504-001, Brazil. pamellaramona@yahoo.com.br.
authors.forename: Pamella Ramona Moraes
authors.initials: PR
authors.lastname: de Souza
authors.affiliation: School of Physical Education and Sport, University of São Paulo, São Paulo, 05508-900, Brazil. guimaraesfabiana@hotmail.com.
authors.forename: Fabiana de Salvi
authors.initials: Fde S
authors.lastname: Guimarães
authors.affiliation: School of Physical Education and Sport, University of São Paulo, São Paulo, 05508-900, Brazil. luizbozi@hotmail.com.
authors.forename: Luiz Henrique Marchesi
authors.initials: LH
authors.lastname: Bozi
authors.affiliation: School of Physical Education and Sport, University of São Paulo, São Paulo, 05508-900, Brazil. pcbrum@usp.br.
authors.forename: Patricia Chakur
authors.initials: PC
authors.lastname: Brum
authors.affiliation: Biosciences Department, Federal University of São Paulo, Santos, 11015-020, Brazil. a.medeiros@unifesp.br.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Medeiros
mesh_terms: D000818:Animals; D003094:Collagen / Q000378:metabolism; D019587:Dietary Supplements; D005080:Exercise Test; D017079:Exercise Tolerance / Q000187:drug effects*; D055551:HSP27 Heat-Shock Proteins / Q000378:metabolism; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006333:Heart Failure / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology; D007930:Leucine / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D010805:Physical Conditioning, Animal / Q000502:physiology*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D017510:Protein Folding / Q000187:drug effects; D013564:Sympathetic Nervous System
chemical_list: D055551:HSP27 Heat-Shock Proteins; D003094:Collagen; D046988:Proteasome Endopeptidase Complex; D007930:Leucine
keywords: aerobic exercise training; cardiac remodeling; heart failure; leucine