Citrulline modulates muscle protein synthesis via S6R and P70S6kinase1 activation in old malnourished rats

Introduction: It has been observed that citrulline (CIT) is an activator of muscle protein synthesis in aged malnourished rats. However, the underlying mechanism is not known. The rate of protein synthesis is regulated in part by amino acids (i.e. leucine [LEU]) at the level of the mammalian Target Of Rapamycin (mTOR) pathway. The aim of this work is to evaluate the ability of CIT to modulate mTOR pathway in a model of aged malnourished rats. Material and methods: Thirty aged (19 month‐old) rats were submitted to dietary restriction (50 % of the spontaneous food intake) during 12 weeks. They were then randomized in 3 groups: 10 rats (R group) were killed and 20 other were refed (at 90 % of the spontaneous food intake) for 1 week with a standard diet (R+NEAA) or a CIT‐supplemented diet (5g/kg/d) (R+CIT). The refed groups received isonitrogenous nutrition thanks to addition of non‐essential AA (NEAA) to the control group. An additional group was an absolute control group: healthy old rats fed ad libitum (AL) Animals were sacrificed at postabsorptive state, and the tibialis (T) muscle was removed. P70S6K1 and S6R phosphorylation were determined by Western Blot. Results: Conclusion: For the first time the ability of a non proteic amino acid to activate mTOR pathway is demonstrated. This suggest that CIT could be a major player in the control of nitrogen homeostasis. This work was supported by funds from the Ministry of Research and Technology