Hypertrophy-Promoting Effects of Leucine Supplementation and Moderate Intensity Aerobic Exercise in Pre-Senescent Mice

Zhi Xia, Jason Cholewa, Yan Zhao, Yue-Qin Yang, Hua-Yu Shang, Lucas Guimarães-Ferreira, Marshall Alan Naimo, Quan-Sheng Su, Nelo Eidy Zanchi

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)
33 Downloads (Pure)


Several studies have indicated a positive influence of leucine supplementation and aerobic training on the aging skeletal muscle signaling pathways that control muscle protein balance and muscle remodeling. However, the effect of a combined intervention requires further clarification. Thirteen month old CD-1(®) mice were subjected to moderate aerobic exercise (45 min swimming per day with 3% body weight workload) and fed a chow diet with 5% leucine or 3.4% alanine for 8 weeks. Serum and plasma were prepared for glucose, urea nitrogen, insulin and amino acid profile analysis. The white gastrocnemius muscles were used for determination of muscle size and signaling proteins involved in protein synthesis and degradation. The results show that both 8 weeks of leucine supplementation and aerobic training elevated the activity of mTOR (mammalian target of rapamycin) and its downstream target p70S6K and 4E-BP1, inhibited the ubiquitin-proteasome system, and increased fiber cross-sectional area (CSA) in white gastrocnemius muscle. Moreover, leucine supplementation in combination with exercise demonstrated more significant effects, such as greater CSA, protein content and altered phosphorylation (suggestive of increased activity) of protein synthesis signaling proteins, in addition to lower expression of proteins involved in protein degradation compared to leucine or exercise alone. The current study shows moderate aerobic training combined with 5% leucine supplementation has the potential to increase muscle size in fast-twitch skeletal muscle during aging, potentially through increased protein synthesis and decreased protein breakdown.

Original languageEnglish
Article number246
Number of pages16
Issue number5
Publication statusPublished - 2 May 2016
Externally publishedYes

Bibliographical note

This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).


  • Aging/drug effects
  • Animals
  • Diet
  • Dietary Supplements
  • Leucine/administration & dosage
  • Male
  • Mice
  • Muscle, Skeletal/drug effects
  • Physical Conditioning, Animal/physiology


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