Effects of resistance exercise with and without creatine supplementation on gene expression and cell signalling in human skeletal muscle Authors

To test the hypothesis that creatine supplementation would enhance the anabolic responses of muscle cell signalling and gene expression to exercise, we studied nine subjects who received either creatine or a placebo (maltodextrin) for 5d in a doubleblind fashion before undergoing muscle biopsies: at rest; immediately after exercise (10×10 repetitions of one leg-extension at 80% 1-RM); and 24h and 72h later (all in the morning after fasting overnight). Creatine supplementation decreased the phosphorylation state of protein kinase B (PKB) on Thr308 at rest by 60% (P<0.05) and that of eukaryotic initiation factor 4E-binding protein on Thr37/46 (4E-BP1) by 30% 24h post-exercise (P<0.05). Creatine increased mRNA for collagen 1(α1), glucose transporter-4 (GLUT-4) and myosin heavy chain I at rest by 250%, 45% and 80% respectively, and myosin heavy chain IIA (MHCIIA) mRNA immediately after exercise by 70% (all P<0.05). Immediately after exercise, and independent of creatine, mRNA for muscle atrophy F-box (MAFbx), MHCIIA, peroxisome proliferator-activated receptor γ coactivator-1α and interleukin-6 were up-regulated (60-350%, P<0.05); the phosphorylation state of p38 both in the sarcoplasm and nucleus were increased (12 and 25 fold respectively, both P<0.05). Concurrently, the phosphorylation states of PKB (Thr308) and 4E-BP1 (Thr37/46) were decreased by 50% and 75% respectively (P<0.05). Twenty-four hours post-exercise, MAFbx, myostatin and GLUT-4 mRNA expression decreased below pre-exercise values (-35 to -50%, P<0.05); calpain 1 mRNA increased 70% 72h post-exercise (P<0.05) and at no other time. In conclusion, 5d of creatine supplementation does not enhance anabolic signalling but increases the expression of certain targeted genes. Page 2 of 34