Bases metabólicas do crescimento muscular

Autores

  • Rodrigo Minoru Manda UNESP
  • Roberto Carlos Burini UNESP

DOI:

https://doi.org/10.33233/rbfe.v9i1.3468

Resumo

O músculo esquelético é o maior tecido do corpo e guarda relação com a autonomia somatocinética e homeostase metabólica. A miogênese é decorrente da predominância de fatores protéicos miogênicos sobre miostáticos. O crescimento ocorre predominantemente de forma hipertrófica, após o nascimento, pelo predomí­nio da sí­ntese sobre o catabolismo protéico. A sí­ntese protéica é finamente mantida por cascata de quinases controladas ou controladoras da mTOR. A mTOR controla o complexo iniciador da sí­ntese protéica, sendo influenciada pela contração muscular, fatores de crescimento e a leucina. O estado de privação energética (↑ AMP/ATP) inibe a mTOR pelo aumento da AMPK. A sí­ntese protéica miofibrilar é estimulada por fatores hidratantes celulares (glicose, insulina, creatina, BCAA, glutamina). Seguindo-se a lesão e necrose miofibrilar, há resposta inflamatória e ação dos fagócitos, promovendo a fagocitose tecidual. Posteriormente, os macrófagos alteram seu fenótipo para resolver a inflamação e promover a miogênese e crescimento miofibrilar.

Palavras-chave: músculo esquelético, hipertrofia muscular, anabolismo protéico, mTOR, regeneração muscular.

Biografia do Autor

Rodrigo Minoru Manda, UNESP

Biomédico, Laboratório em Metabolismo Nutricional e Desportivo, Faculdade de Medicina de Botucatu (UNESP)

Roberto Carlos Burini, UNESP

Professor Titular do Departamento de Saúde Pública da Faculdade de Medicina de Botucatu (UNESP) e responsável pelo CeMENutri

Referências

Robergs RA, Roberts SO. Função neuromuscular e adaptação ao exercício. In: Princípios fundamentais de fisiologia do exercício para adaptação, desempenho e saúde. 1ª ed. São Paulo: Phorte; 2002. p.76-109.

Nair KS. Aging muscle. Am J Clin Nutr 2005;81:953-63.

Mascher H, Tannerstedt J, Brink-Elfegoun T, Ekblom B, Gustafsson T, Blomstrand E. Repeated resistance exercise training induces different changes in mRNA expression of MAFbx and MuRF-1 in human skeletal muscle. Am J Physiol Endocrinol Metab 2008;294:E43-51.

Leger B, Cartoni R, Praz M, Lamon S, Dériaz O, Crettenand A, et al. Akt signalling through GSK-3beta, mTOR and Foxo1 is involved in human skeletal muscle hypertrophy and atrophy. J Physiol 2006;576:923-33.

Welle S, Bhatt K, Thornton CA. Stimulation of myofibrillar synthesis by exercise is mediated by more efficient translation of mRNA. J Appl Physiol 1999;86:1220-5.

Witard OC, Tieland M, Beelen M, Tipton KD, van Loon LJ, Koopman R. Resistance exercise increases postprandial muscle protein synthesis in humans. Med Sci Sports Exerc 2009;41:144-54.

Mitchell JW, Nadel ER, Stolwijk JA. Respiratory weight losses during exercise. J Appl Physiol 1972;32:474-6.

Anthony JC, Anthony TG, Kimball SR, Jefferson LS. Signaling pathways involved in translational control of protein synthesis in skeletal muscle by leucine. J Nutr 2001;131:856S-860S.

Fingar DC, Blenis J. Target of rapamycin (TOR): an integrator of nutrient and growth factor signals and coordinator of cell growth and cell cycle progression. Oncogene 2004;23:3151-71.

Kimball SR, Farrell PA, Jefferson LS. Invited Review: Role of insulin in translational control of protein synthesis in skeletal muscle by amino acids or exercise. J Appl Physiol 2002;93:1168-80.

Oshiro N, Takahashi R, Yoshino K, Tanimura K, Nakashima A, Eguchi S, et al. The proline-rich Akt substrate of 40 kDa (PRAS40) is a physiological substrate of mammalian target of rapamycin complex 1. J Biol Chem 2007;282:20329-39.

Proud CG. Amino acids and mTOR signalling in anabolic function. Biochem Soc Trans 2007;35:1187-90.

Pruznak AM, Kazi AA, Frost RA, Vary TC, Lang CH. Activation of AMP-activated protein kinase by 5-aminoimidazole-4-carboxamide-1-beta-D-ribonucleoside prevents leucine-stimulated protein synthesis in rat skeletal muscle. J Nutr 2008;138:1887-94.

Lang CH, Frost RA, Jefferson LS, Kimball SR, Vary TC. Endotoxin-induced decrease in muscle protein synthesis is associated with changes in eIF2B, eIF4E, and IGF-I. Am J Physiol Endocrinol Metab 2000;278:E1133-43.

Svanberg E, Frost RA, Lang CH, Isgaard J, Jefferson LS, Kimball, et al. IGF-I/IGFBP-3 binary complex modulates sepsis-induced inhibition of protein synthesis in skeletal muscle. Am J Physiol Endocrinol Metab 2000;279:E1145-58.

Huang J, Manning BD. The TSC1-TSC2 complex: a molecular switchboard controlling cell growth. Biochem J 2008;412:179-90.

American College of Sports Medicine position stand. Progression models in resistance training for healthy adults. Med Sci Sports Exerc 2009;41:687-708.

Roth SM, Ferrell RE, Peters DG, Metter EJ, Hurley BF, Rogers MA. Influence of age, sex, and strength training on human muscle gene expression determined by microarray. Physiol Genomics 2002;10:181-90.

Roth SM, Martel GF, Ferrell RE, Metter EJ, Hurley BF, Rogers MA. Myostatin gene expression is reduced in humans with heavy-resistance strength training: a brief communication. Exp Biol Med (Maywood) 2003;228:706-9.

Phillips SM, Tipton KD, Aarsland A, Wolf SE, Wolfe RR. Mixed muscle protein synthesis and breakdown after resistance exercise in humans. Am J Physiol 1997;273:E99-107.

MacDougall JD, Gibala MJ, Tarnopolsky MA, MacDonald JR, Interisano SA, Yarasheski KE. The time course for elevated muscle protein synthesis following heavy resistance exercise. Can J Appl Physiol 1995;20:480-6.

Moritani T, deVries HA. Neural factors versus hypertrophy in the time course of muscle strength gain. Am J Phys Med 1979;58:115-30.

Phillips SM. Short-term training: when do repeated bouts of resistance exercise become training? Can J Appl Physiol 2000;25:185-93.

Miyazaki M, Noguchi M, Takemasa T. Intermittent reloading attenuates muscle atrophy through modulating Akt/mTOR pathway. Med Sci Sports Exerc 2008;40:848-55.

Biolo G, Tipton KD, Klein S, Wolfe RR. An abundant supply of amino acids enhances the metabolic effect of exercise on muscle protein. Am J Physiol 1997;273:E122-9.

Fujita S, Dreyer HC, Drummond MJ, Micah J, Glynn EL. Nutrient signaling in the regulation of human muscle protein synthesis. J Physiol 2007;582:813-23.

Kraemer WJ, Ratamess NA. Hormonal responses and adaptations to resistance exercise and training. Sports Med 2005;35:339-61.

Kubica N, Bolster DR, Farrell PA, Kimball SR, Jefferson LS. Resistance exercise increases muscle protein synthesis and translation of eukaryotic initiation factor 2Bepsilon mRNA in a mammalian target of rapamycin-dependent manner. J Biol Chem 2005;280:7570-80.

Roth E. Skeletal muscle gain: how much can be achieved by protein and amino acid administration? Curr Opin Clin Nutr Metab Care 2008;11:32-3.

Drummond MJ, Rasmussen BB. Leucine-enriched nutrients and the regulation of mammalian target of rapamycin signalling and human skeletal muscle protein synthesis. Curr Opin Clin Nutr Metab Care 2008;11:222-6.

Rieu I, Balage M, Sornet C, et al. Leucine supplementation improves muscle protein synthesis in elderly men independently of hyperaminoacidaemia. J Physiol 2006;575:305-15.

Rivas DA, Lessard SJ, Yaspelkis BB, Hawley JA. Regulation of mTORC 1/2 formation in response to a high- fat diet and exercise training. Med Sci Sports Exerc 2008;40(5):S3-S4.

Hardie DG, Sakamoto K. AMPK: a key sensor of fuel and energy status in skeletal muscle. Physiology (Bethesda) 2006;21:48-60.

Gwinn DM, Shackelford DB, Egan DF, Mihaylova MM, Mery A, Vasques DS, et al. AMPK phosphorylation of raptor mediates a metabolic checkpoint. Mol Cell 2008;30:214-26.

Bolster DR, Crozier SJ, Kimball SR, Jefferson LS. AMP-activated protein kinase suppresses protein synthesis in rat skeletal muscle through down-regulated mammalian target of rapamycin (mTOR) signaling. J Biol Chem 2002;277:23977-80.

Dreyer HC, Fujita S, Cadenas JG, Chinkes DL, Volpi E, Rasmussen BB. Resistance exercise increases AMPK activity and reduces 4E-BP1 phosphorylation and protein synthesis in human skeletal muscle. J Physiol 2006;576:613-24.

Koopman R, Zorenc AH, Gransier RJ, Cameron-Smith D, van Loon LJ. Increase in S6K1 phosphorylation in human skeletal muscle following resistance exercise occurs mainly in type II muscle fibers. Am J Physiol Endocrinol Metab 2006;290:E1245-52.

Chazaud B, Brigitte M, Yacoub-Youssef H, Arnold L, Gherardi R, Sonnet C et al. Dual and beneficial roles of macrophages during skeletal muscle regeneration. Exerc Sport Sci Rev 2009;37:18-22.

Stout RD, Suttles J. Functional plasticity of macrophages: reversible adaptation to changing microenvironments. J Leukoc Biol 2004;76:509-13.

Arnold L, Henry A, Poron F, van Rooijen N, Plonquet A, Gherardi RK et al. Inflammatory monocytes recruited after skeletal muscle injury switch into antiinflammatory macrophages to support myogenesis. J Exp Med 2007;204:1057-69.

Gordon S, Taylor PR. Monocyte and macrophage heterogeneity. Nat Rev Immunol 2005;5:953-64.

Li YP. TNF-alpha is a mitogen in skeletal muscle. Am J Physiol Cell Physiol 2003;285:C370-6.

Lefaucheur JP, Gjata B, Lafont H, Sebille A. Angiogenic and inflammatory responses following skeletal muscle injury are altered by immune neutralization of endogenous basic fibroblast growth factor, insulin-like growth factor-1 and transforming growth factor-beta 1. J Neuroimmunol 1996;70:37-44.

Bondesen BA, Mills ST, Pavlath GK. The COX-2 pathway regulates growth of atrophied muscle via multiple mechanisms. Am J Physiol Cell Physiol 2006;290:C1651-9.

Shen W, Li Y, Zhu J, Schwendener R, Huard J. Interaction between macrophages, TGF-beta1, and the COX-2 pathway during the inflammatory phase of skeletal muscle healing after injury. J Cell Physiol 2008;214:405-12.

Boppart MD, Liu J, Alexander NM, Kaufman SJ. The alpha7beta1 integrin recruits a Sca-1+/CD45- stem cell population in skeletal muscle following exercise-induced injury. Med Sci Sports Exerc 2008;40(5):S33.

Moore NA, Devaney JM, Hoffman E, Zambraski E, Gordish H, Clarkson PM. Association of Akt2 genotypes and exercise muscle damage. Med Sci Sports Exerc 2008;40(5):S32.

Washington TA, Davis JM, Lowe LL, Wilson LB, Durstine JL, Carson JA. Interleukin-6 deficiency attenuates the recovery of gastrocnemius muscle mass from disuse-induced atrophy. Med Sci Sports Exerc 2008;40(5).

Carey AL, Bruce CR, Sacchetti M, Anderson MJ, Olsen DB, Saltin B, et al. Interleukin-6 and tumor necrosis factor-alpha are not increased in patients with Type 2 diabetes: evidence that plasma interleukin-6 is related to fat mass and not insulin responsiveness. Diabetologia 2004;47:1029-37.

Pedersen BK, Fischer CP. Beneficial health effects of exercise--the role of IL-6 as a myokine. Trends Pharmacol Sci 2007;28:152-6.

Mehan RS, Allen DL, Uyenishi J, Cleary A, Lindsay SF, Reed JM. Transcriptional regulation of interleukin-6 expression in mouse skeletal muscle in vivo and in myotubes in viitro. Med Sci Sports Exerc 2008;40(5):S163-S164.

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Publicado

2010-03-10

Edição

v. 9 n. 1 (2010): Fisiologia do Exercí­cio v9n1

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