Long-term quercetin dietary enrichment decreases muscle injury in mdx mice. Clinical Nutrition, June 21, 2014. Katrin Hollinger a; R. Andrew Shanely b, c; John C. Quindry d; Joshua T. Selsby a.
a Department of Animal Science, Iowa State University; b. Human Performance Laboratory, Appalachian State University, North Carolina Research Campus; Appalachian State University, College of Health Sciences, Boone, NC; d School of Kinesiology, Auburn University, Auburn, AL
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-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.
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.
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.
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.