A comparison of the effects of ursolic acid and L-leucine supplementation on markers of muscle protein synthesis via Akt-mTOR signaling response to resistance exercise.




Church, David D.

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Resistance exercise (RE) stimulates skeletal muscle protein synthesis (MPS) during post-exercise recovery due to up-regulation of the mammalian target of rapamycin (mTOR) signaling pathway L-leucine supplementation is also known to stimulate MPS by activating mTOR signaling. However, recent research has discovered a natural compound called ursolic acid which also appears to stimulate MPS by activating the mTOR signaling pathway, and has been presumed to occur due to IGF-1 receptor (IGF-1R) up-regulation. Ursolic acid is a natural pentacyclic triterpenoid carboxylic acid that is widely found in apple skin and other fruits such as cranberries. The main purpose of this study was to compare the effects of a single dose of ursolic acid or L-leucine supplementation given immediately after resistance exercise on IGF-1 (a serum regulator of MPS) and the subsequent effects of IGF-1 on phosphorylating/activating its receptor (IGF-1R^Tyr1131). Furthermore, the purpose was to also determine the effects on signaling intermediates of MPS contained within the Akt/mTOR pathway (phosphorylated levels of Akt^Thr308, mTOR^Ser2448, p70S6K^Thr389). In a randomized, cross-over design, nine apparently healthy, resistance-trained [regular, consistent resistance training (i.e. thrice weekly) for at least 1 year prior to the onset of the study], men between the ages of 18-30 performed three separate testing sessions of lower-body resistance exercise involving 4 sets of 8-10 repetitions at 75-80% 1-RM on the angled leg press and knee extension exercises. Immediately after each resistance exercise session, participants orally ingested 3 grams (0.043 g/kg equivalent) of cellulose placebo (PLC), L-leucine (LEU), or ursolic acid (UA). A venous blood sample was obtained before, and 0.5, 2, and 6 hr post-exercise, whereas a vastus lateralis muscle biopsy was obtained before and 2 and 6 hr post-exercise. Each testing session was separated by 7 days to allow full recovery between sessions. Statistical analyses were performed utilizing separate two-way ANOVA for each criterion variable employing a probability level of ≤ 0.05. Using ELISA, no significant differences were observed among the three supplements for serum IGF-1 (p> 0.05). Also using ELISA, for skeletal muscle phosphoproteins, no significant differences existed among the three supplements for phosphorylated IGF-1R, Akt, and p70S6K (p> 0.05). However, the LEU supplement significantly increased phosphorylated mTOR compared to UA and PLC (p= 0.001). At the 3 g dose provided, ursolic acid was unable to increase IGF-1R signaling and, unlike L-leucine, ursolic acid had no positive effect on mTOR signaling activity. Therefore, ursolic acid appears to have no effect on mTOR activity when ingested immediately following resistance exercise.



Muscle protein synthesis., mTOR signalling pathway., Resistance training., Ursolic acid., Leucine.