L‐carnitine supplement and running training improve skeletal muscle recovery after hindlimb suspension induced muscle atrophy

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Several studies demonstrated that endurance exercise has an effect on protein synthesis through the activation of Akt1/mTOR pathway. Along with Akt1/mTOR pathway, PGC‐1α effects on protein synthesis through the inhibition of muscle specific E3 ligases expression such as atrogin‐1 and MuRF1. PGC‐1α expression in skeletal muscle can be induced by a stimulus of endurance exercise. Recently, L‐carnitine down‐regulates atrogin‐1 and MuRF1 mRNA expression and reduces muscle wasting in a rat model of cancer cachexia. Also, L‐carnitine supplement can increase the level of IGF‐1, which in turn activates the downstream Akt1/mTOR signaling pathway. Altogether, these findings suggest that L –carnitine and combined with running exercise could promote muscle recovery after disuse induced muscle atrophy through the inhibition of E3 ligases expression and Akt1/mTOR pathway activation. However, the effect of LC supplement in growing rats on muscle atrophy and recovery of muscle mass combined with running exercise after muscle atrophy induced by disuse has not yet been reported. Therefore, the purpose of this study was to clarify whether L‐carnitine supplement and combined with running exercise improve muscle mass recovery after disuse induced muscle atrophy through the inhibition of UPP and activation of Ak1/mTOR pathway. Male Wistar rats were randomly assigned to 4 groups; sedentary after hindlimb suspension with 1,250 mg/kg casein supplement group (Sed‐Con), sedentary after hindlimb suspension with 1,250 mg/kg l‐carnitine supplement group (Sed‐Car), running exercise after hindlimb suspension with 1,250 mg/kg casein supplement group(Ex‐Con), and running exercise after hindlimb suspension with 1,250 mg/kg l‐carnitine supplement group (Ex‐Car) for 4wk. Soleus muscle significantly greater in exercised groups compared to sedentary groups. MuRF1 mRNA expression is significantly decreased by L‐carnitine supplement in sedentary and exercise groups. PGC‐1α and Akt1 mRNAs expression in muscle is significantly increased by the exercise and L‐carnitine supplement. However, PGC‐1α protein expression is significantly increased in Ex‐Car group compared to Sed‐Con group. mTOR mRNA expression is only increased in Ex‐Car group groups compared to the Sed‐Con group. In conclusion, the main findings of this study is that L‐carnitine combined running exercise enhanced the muscle recovery after hindlimb suspension induced muscle atrophy in soleus muscle possibly through of the increased expression of PGC‐1α by inhibiting the muscle specific E3 ligases expression and activation of Akt1/mTOR pathway. These results provide important information that understanding of the mechanisms underlying muscle recovery after hindlimb suspension induced muscle atrophy by the L‐carnitine combined with running exercise.