Does muscle damage promote hypertrophy? The fall of a paradigm supported by integrated muscle protein synthesis analysis

Author(s)

Felipe Romano Damas Nogueira

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Escola de Educação Física e Esportes (EEFE/BT)
• Defense date: 2017-04-27

Examining board members

Carlos Ugrinowitsch; Renato Barroso da Silva; Valmor Alberto Augusto Tricoli; Marco Carlos Uchida

• Advisor: Carlos Ugrinowitsch

Abstract

Skeletal muscle hypertrophy is one of the main outcomes of resistance training (RT), but how hypertrophy is modulated and the mechanisms regulating it are not fully understood. To investigate how muscle hypertrophy is modulated during RT and the mechanisms that underpin it, we measured in 10 young men (27[1] years, 24[1] kg·m-2) at the beginning (T1), at the third week (T2), and tenth week (T3) of RT: 1) vastus lateralis cross-sectional area (CSA) and the echo intensity by ultrasound; 2) day-to-day (24h and 48h) integrated myofibrillar protein synthesis (MPS), after maximal resistance exercise (RE) using deuterium-oxide ingestion and muscle biopsies; 3) RE-induced muscle damage by analyzing Z-line streaming and indirect markers; 4) type I and II fiber CSA (fCSA), modulations in satellite cells pool and in myonuclear number and domain by immunohistological analyses; 5) global gene expression by microarray. Main results show that there was significant (P<0.04) muscle hypertrophy (increase in muscle CSA and type II fCSA) only in T3 (increases in muscle CSA in T2 were considered edema through echo intensity analyses). Changes in MPS post-RE at T1, T2 and T3 were greater at T1 (P<0.03) than at T2 and T3 (similar values between T2 and T3). Muscle damage was the highest during post-RE recovery at T1, attenuated at T2 and further attenuated at T3. Changes in MPS post-RE at both T2 and T3, but not at T1, were strongly correlated (r~0.9, P<0.04) with muscle hypertrophy (T3-T1). Satellite cells pool markedly increased 48h post-RE only in T1, and remained chronically elevated (P<0.05). There was no significant change in myonuclear number or domain during RT. The microarray analysis indicated improved metabolic efficiency, improved stress response and attenuated muscle damage, and strengthening of muscle structures involving myofibrillar proteins and extracellular matrix. Initial MPS response post-RE in a RT program is not directed to support muscle hypertrophy, coinciding with the highest magnitude of muscle damage. However, integrated MyoPS is quickly \'refined\', and with the progressive attenuation on muscle damage by 3wk of RT (T2), MPS is related to muscle hypertrophy (also at T3). We conclude that muscle hypertrophy is the result of accumulated intermittent changes in MPS post-RE in RT, which coincides with progressive muscle damage attenuation. The absence of change in myonuclei number indicates that preexisting myonuclei were able to expand post-RE MPS to promote muscle hypertrophy. Initial expansion in satellite cells pool, chronically maintained, favors a regeneration purpose of satellite cells in response to muscle damage and an anticipatory \"readiness\" state rather than a direct role in muscle hypertrophy, at least for the first 10 weeks of RT in young men (AU)

• FAPESP's process: 12/24499-1 - The role of the magnitude of muscle damage in hypertrophic responses
• Grantee: Felipe Romano Damas Nogueira
• Support Opportunities: Scholarships in Brazil - Doctorate