Skeletal muscles express multiple nuclear receptors. However, their role in muscular dystrophy is unknown. Recently, we found that transgenic mice over-expressing nuclear receptor PPAR-delta in skeletal muscles ran twice as long and as far as non-transgenic mice on a treadmill [Transgenic/non-transgenic; time: 140 min/80 min; distance: 1800 m/800 m]. Such an improvement in skeletal muscle performance on activating PPAR-delta may be beneficial in dystrophic muscles, which are characterized by weakness and fatigue. In this proposal we will test the hypothesis that activation of PPAR-delta decreases the pathology of Duchenne muscular dystrophy (DMD). All the experiments related to the hypothesis will be performed in mdx mice, a rodent model of DMD. In brief, we will measure the suppressive effect of both PPAR-delta agonist (GW1516) treatment and muscle specific PPAR-delta over-expression on the pathological biomarkers of DMD in mdx mice at the level of muscle morphology, gene expression and contractile properties. The results from our study will reveal whether PPAR-delta is an appropriate target to counteract DMD as well as whether an orally active PPAR-delta agonist can decrease the pathology of DMD. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32AR053803-01
Application #
7114001
Study Section
Special Emphasis Panel (ZRG1-F10-H (20))
Program Officer
Boyce, Amanda T
Project Start
2006-06-01
Project End
2009-05-31
Budget Start
2006-06-01
Budget End
2007-05-31
Support Year
1
Fiscal Year
2006
Total Cost
$50,428
Indirect Cost
Name
Salk Institute for Biological Studies
Department
Type
DUNS #
078731668
City
La Jolla
State
CA
Country
United States
Zip Code
92037
Narkar, Vihang A; Fan, Weiwei; Downes, Michael et al. (2011) Exercise and PGC-1?-independent synchronization of type I muscle metabolism and vasculature by ERR?. Cell Metab 13:283-93
Matsakas, Antonios; Narkar, Vihang A (2010) Endurance exercise mimetics in skeletal muscle. Curr Sports Med Rep 9:227-32
Narkar, Vihang A; Downes, Michael; Yu, Ruth T et al. (2008) AMPK and PPARdelta agonists are exercise mimetics. Cell 134:405-15