Title page for ETD etd-02042010-115033


Type of Document Dissertation
Author Voelker, Kevin Andrew
Author's Email Address kevoelke@vt.edu
URN etd-02042010-115033
Title Leucine and exercise improve skeletal muscle function in the mdx mouse
Degree PhD
Department Human Nutrition, Foods, and Exercise
Advisory Committee
Advisor Name Title
Grange, Robert W. Committee Chair
Davy, Kevin P. Committee Member
Hutson, Susan M. Committee Member
Newton, William E. Committee Member
Ward, Christopher W. Committee Member
Keywords
  • Leucine
  • mdx
  • Muscular Dystrophy
  • Calpains
  • mTOR
  • Skeletal Muscle
Date of Defense 2010-01-21
Availability restricted
Abstract
Duchene muscular dystrophy (DMD) is a lethal X-linked disease that afflicts approximately 1 in 3500 newborn males. Boys with DMD will become progressively weaker causing wheelchair dependence by their early teens and death by their mid to late twenties. Currently there is no cure for DMD, the exact mechanism of disease action remains elusive, and treatments to improve quality of life are limited. Two areas of DMD research that could begin to fill this void and provide simple, cost effective therapy aimed to improve quality of life are neutriceutical and exercise therapies.

We hypothesized that leucine, a branched chain amino acid (BCAA) with anabolic properties, given to sedentary and exercised x-linked dystrophic mice (mdx) over 4 weeks would improve skeletal muscle function and decrease markers of skeletal muscle degradation. In sedentary mdx mice, leucine improved tetanic extensor digitorum longus (EDL) stress (p < 0.05), gastrocnemius mammalian target or rapamycin (mTOR) phosphorylation (p < 0.05), while decreasing the rate of real-time calpain activity in flexor digitorum brevis (FDB) fibers (p < 0.05) compared to sedentary mice given no leucine. In exercised mdx mice, leucine improved total running distance over the 4 week testing period by 40% (p < 0.02) and increased EDL stress at every frequency recorded (p < 0.05).

Our data lead us to the conclusion that the BCAA leucine can increase EDL muscle stress in dystrophic animals, and that the effects of leucine treatment are enhanced when leucine supplementation is combined with exercise. Leucine supplementation should be explored further and in higher order species of muscular dystrophy to determine if its use could provide clinical improvements in DMD patients.

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