alexa Abstract | Substrate Metabolism and Mitochondrial Function in Skeletal Muscle of Amyloid Precursor Protein-Overexpressing Mice

Annals of Clinical and Laboratory Research
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Background: Sporadic Inclusion body myositis (sIBM) is an idiopathic inflammatory myopathy that involves inflammation and damage to skeletal muscle tissue. Studies in humans demonstrate altered mitochondrial morphology in skeletal muscle from patients diagnosed with sIBM suggesting mitochondrial defects may be a significant contributor to disease progression.

Methods: MCK-APP mice, overexpress amyloid precursor protein specifically in skeletal muscle, display characteristics of sIBM, and are an accepted model to study disease pathology.

Results: The current studies demonstrate a significant reduction in fat oxidation and oxidative efficiency in white gastrocnemius muscle in 9-month-old MCKAPP. However, there were no differences in mitochondrial bioenergetics or the production of reactive oxygen species in red or white gastrocnemius muscle in 3, 6, or 9-month-old MCK-APP mice compared to wild-type littermates.

Conclusion: Functional alterations in mitochondria are not yet pronounced in 3, 6, and 9-month-old MCK-APP mice prior to symptom development; however alterations in substrate metabolism in white skeletal muscle may be present.

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Author(s): Elika Shabrokh John Kavanaugh Ryan McMillan Yaru Wu Matt Hulver and Madlyn Frisard


Amyloid precursor protein, Amyloid beta, Bioenergetics, Fatty acid oxidation, Mitochondrial metabolism, Skeletal muscle metabolism, Reactive oxygen species, Clinical biochemistry, Investigational new drug, Clinical Trial

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