Regulation of muscle cell differentiation and growth by nutrients and exercise

• Main Author: Deldicque, Louise
• Format: Others
• Language: en
• Published: Universite catholique de Louvain 2007
• Subjects: Cell signalling; Glutamine; Leucine; Western blot; RTQ-PCR
• Online Access: http://edoc.bib.ucl.ac.be:81/ETD-db/collection/available/BelnUcetd-11282007-143752/

A significant advance in understanding skeletal muscle adaptation to physical training has been the observation that nutrients and exercise work in synergy to enhance muscle protein synthesis. Physical activity triggers an adaptive response to which nutrition provides the necessary building blocks for an optimal response. The aim of the present work was to contribute to the understanding of the molecular events induced by exercise or nutrients (creatine and amino acids) to create the adaptive environment and to induce the cellular adaptation and growth, respectively. From a methodological point of view, two experimental models were used: muscle biopsies taken from the vastus lateralis of human volunteers and myotubes cultured from C2C12 cells. The transcription of a series of genes involved in muscle remodelling (MAFbx, MHCIIA, PGC-1á, PCNA and IL-6) was increased immediately after the completion of a resistance exercise session performed in the fasted state. The phosphorylation state of p38 and ERK1/2 was also increased, whereas the Akt/PKB pathway was negatively regulated. This contrasted with the high phosphorylation state observed on p70s6k and 4E-BP1 when subjects received a large amount of amino acids during the recovery period. Our results suggest that the MAPK pathway can be triggered by contractile activity alone, whereas the Akt/PKB pathway requires nutrients to be activated. Certain amino acids regulate the phosphorylation state of mTOR and its downstream targets, as demonstrated by one of our in vitro studies. However, that modulation did not lead to a systematic modification in the rate of protein synthesis. Amino acids were also able to influence the expression of muscle-specific genes, highlighting their importance in the control of muscle protein synthesis. Protein anabolism was largely enhanced and cell differentiation was accelerated by creatine in our in vitro model. We have identified the p38 and Akt/PKB pathways as mediators of these effects. Nevertheless, we were unable to confirm the existence of similar events in human skeletal muscle in vivo.