l-Leucine Increases Skeletal Muscle IGF-1 but Does Not Differentially Increase Akt/mTORC1 Signaling and Serum IGF-1 Compared to Ursolic Acid in Response to Resistance Exercise in Resistance-Trained Men

J Am Coll Nutr. Sep-Oct 2016;35(7):627-638. doi: 10.1080/07315724.2015.1132019. Epub 2016 Jun 22.


Objective: Ursolic acid administration following resistance exercise increases mammalian target of rapamycin complex 1 (mTORC1) activity and skeletal muscle IGF-1 concentration in murines in a manner similar to l-leucine yet remains unexamined in humans. This study examined serum and skeletal muscle insulin-like growth factor-1 (IGF-1) and Akt/mTORC1 signaling activity following ingestion of either ursolic acid or l-leucine immediately after resistance exercise.

Methods: Nine resistance-trained men performed 3 lower-body resistance exercise sessions involving 4 sets of 8-10 repetitions at 75%-80% one repetition maximum (1-RM) on the angled leg press and knee extension exercises. Immediately following each session, participants orally ingested 3 g cellulose placebo (PLC), l-leucine (LEU), or ursolic acid (UA). Blood samples were obtained pre-exercise and at 0.5, 2, and 6 hours postexercise. Muscle biopsies were obtained pre-exercise and at 2 and 6 hours postexercise.

Results: Plasma leucine increased in LEU at 2 hours postexercise compared to PLC (p = 0.04). Plasma ursolic acid increased in UA at 2 h and 6 hours postexercise compared to PLC and LEU (p < 0.003). No significant differences were observed for serum insulin (p = 0.98) and IGF-1 (p = 0.99) or skeletal muscle IGF-1 receptor (IGF-1R; p = 0.84), Akt (p = 0.55), mTOR (p = 0.09), and p70S6K (p = 0.98). Skeletal muscle IGF-1 was significantly increased in LEU at 2 hours postexercise (p = 0.03) and 6 hours postexercise (p = 0.04) compared to PLC and UA.

Conclusion: Three grams of l-leucine and ursolic acid had no effect on Akt/mTORC1 signaling or serum insulin or IGF-1; however, l-leucine increased skeletal muscle IGF-1 concentration in resistance-trained men.

Keywords: branched-chain amino acid; cell signaling; muscle protein synthesis; resistance exercise.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cross-Over Studies
  • Diet
  • Dietary Supplements
  • Double-Blind Method
  • Humans
  • Insulin / blood
  • Insulin-Like Growth Factor I / analysis*
  • Leucine / administration & dosage*
  • Leucine / blood
  • Male
  • Mechanistic Target of Rapamycin Complex 1
  • Multiprotein Complexes / metabolism*
  • Muscle, Skeletal / chemistry*
  • Muscle, Skeletal / drug effects
  • Resistance Training*
  • Signal Transduction / drug effects
  • TOR Serine-Threonine Kinases / metabolism*
  • Triterpenes / administration & dosage*
  • Triterpenes / blood
  • Young Adult


  • Insulin
  • Multiprotein Complexes
  • Triterpenes
  • Insulin-Like Growth Factor I
  • TOR Serine-Threonine Kinases
  • Mechanistic Target of Rapamycin Complex 1
  • Leucine
  • ursolic acid