title: Long-term quercetin dietary enrichment decreases muscle injury in mdx mice.
abstract: OBJECTIVE
  Duchenne muscular dystrophy results from a mutation in the dystrophin gene, which leads to a dystrophin-deficiency. Dystrophic muscle is marked by progressive muscle injury and loss of muscle fibers. Activation of the PGC-1α pathway has been previously shown to decrease disease-related muscle damage. Oral administration of the flavonol, quercetin, appears to be an effective and safe method to activate the PGC-1α pathway. The aim of this investigation was to determine the extent to which long term dietary quercetin enrichment would decrease muscle injury in dystrophic skeletal muscle. We hypothesized that a quercetin enriched diet would rescue dystrophic muscle from further decline and increase utrophin abundance.
  
  
  METHODS
  Beginning at three-months of age and continuing to nine-months of age mdx mice (n = 10/group) were assigned to either to mdx-control receiving standard chow or to mdx-quercetin receiving a 0.2% quercetin-enriched diet. At nine-months of age mice were sacrificed and costal diaphragms collected. One hemidiaphragm was used for histological analysis and the second hemidiaphragm was used to determine gene expression via RT-qPCR.
  
  
  RESULTS
  The diaphragm from the mdx-quercetin group had 24% (p ≤ 0.05) more muscle fibers/area and 34% (p ≤ 0.05) fewer centrally nucleated fibers compared to the mdx-control group. Further, there were 44% (p ≤ 0.05) fewer infiltrating immune cells/area, a corresponding 31% (p ≤ 0.05) reduction in TNF gene expression, and a near 50% reduction in fibrosis. The quercetin-enriched diet increased expression of genes associated with oxidative metabolism but did not increase utrophin protein abundance.
  
  
  CONCLUSIONS
  Long-term quercetin supplementation decreased disease-related muscle injury in dystrophic skeletal muscle; however the role of PGC-1α pathway activation as a mediator of this response is unclear.
authors.affiliation: Department of Animal Science, Iowa State University, Ames, IA 50011, USA.
authors.forename: Katrin
authors.initials: K
authors.lastname: Hollinger
authors.affiliation: Human Performance Laboratory, Appalachian State University, North Carolina Research Campus, Kannapolis, NC 28081, USA; Appalachian State University, College of Health Sciences, Boone, NC, USA.
authors.forename: R Andrew
authors.initials: RA
authors.lastname: Shanely
authors.affiliation: School of Kinesiology, Auburn University, Auburn, AL 36849, USA.
authors.forename: John C
authors.initials: JC
authors.lastname: Quindry
authors.affiliation: Department of Animal Science, Iowa State University, Ames, IA 50011, USA. Electronic address: jselsby@iastate.edu.
authors.forename: Joshua T
authors.initials: JT
authors.lastname: Selsby
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D016189:Dystrophin / Q000172:deficiency / Q000235:genetics; D015870:Gene Expression; D051379:Mice; D018101:Mice, Inbred mdx; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D020388:Muscular Dystrophy, Duchenne / Q000188:drug therapy*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011794:Quercetin / Q000494:pharmacology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D049411:Utrophin / Q000378:metabolism
chemical_list: D016189:Dystrophin; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D014157:Transcription Factors; D049411:Utrophin; D011794:Quercetin
keywords: Diaphragm; Duchenne muscular dystrophy; Dystrophin; PGC-1α; Resveratrol