Long-term quercetin dietary enrichment decreases muscle injury in mdx mice

ASU Author/Contributor (non-ASU co-authors, if there are any, appear on document)
Andrew Shanely Ph.D, Associate professor (Creator)
Institution
Appalachian State University (ASU )
Web Site: https://library.appstate.edu/

Abstract: Background & aims: 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-1a pathway has been previously shown to decrease disease- related muscle damage. Oraladministration of the flavonol, quercetin, appears to be an effective and safe method to activate the PGC-1a pathway. The aim of this investigation was to determine the extent to which long term dietary quercetin enrichment woulddecrease 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 ¼ 10/ group) were assigned to either to mdx-control receiving standard chow or to mdx-quercetin receiving a 0.2% quercetin-enricheddiet. 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) fewerinfiltrating 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 metabolismbut 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-1a pathway activation as a mediator of this response is unclear.

Additional Information

Publication
Katrin Hollinger, R. Andrew Shanely, John C. Quindry & Joshua T. Selsby (2015) " Long-term quercetin dietary enrichment decreases muscle injury in mdx mice" Clinical Nutrition 34 (2015) Version of Record available @ (http://dx.doi.org/10.1016/j.clnu.2014.06.008)
Language: English
Date: 2015
Keywords
duchenne-muscular-dystrophy, PGC-1a, reseratrol, dystrophin, diaphragm

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