Summary of Study ST000623

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench,, where it has been assigned Project ID PR000455. The data can be accessed directly via it's Project DOI: 10.21228/M8Q415 This work is supported by NIH grant, U2C- DK119886.


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Study IDST000623
Study TitleNon-targeted Metabolomics Analysis of Golden Retriever Muscular Dystrophy-Affected Muscles Reveals Alterations in Arginine and Proline Metabolism, and Elevations in Glutamic and Oleic Acid In Vivo
Study SummaryLike Duchenne muscular dystrophy (DMD), the Golden Retriever Muscular Dystrophy (GRMD) dog model of DMD exhibits is characterized by muscle necrosis, progressive paralysis, and pseudohypertrophy in specific skeletal muscles. This severe GRMD phenotype included atrophy of the biceps femoris (BF) and compared to unaffected normal dogs, while the long digital extensor (LDE) of the pelvic limb, serving as a hip flex and stifle extensor, is unaffected. A recent microarray analysis of GRMD identified alterations in genes associated with lipid metabolism and energy production. We, therefore, undertook a non-targeted metabolomics analysis of the GRMD BF (affected) and LDE (unaffected) using GC-MS to identify underlying metabolic defects specific for affected GRMD skeletal muscle. Of the 134 metabolites identified in BF, eight were significantly altered in GRMD BF compared to control BF (Glutamic Acid (2.48 fold vs. controls); Oleic Acid (1.76 fold vs. controls); Proline (1.73 fold vs. controls); Myoinositol-2- Phosphate (0.44 fold vs. controls); Fumaric Acid (0.40 fold vs. controls); Carnosine (0.40 fold vs. controls); Lactamide (0.33 fold vs. controls); and Stearamide (0.23 fold vs. controls). Pathway analysis of the T-test significant metabolites identified BF muscle metabolites significantly enriched for Arginine and proline metabolism (p=5.8E-4, FDR=0.04) and Alanine, aspartate, and glutamate metabolism (p=1.3E-3, FDR=0.05). The GRMD LDE previously reported to be unaffected, in contrast, had only one significantly altered metabolite (3-Phosphoglyceric Acid (0.35 Fold vs. controls)).The identification of elevated BF Oleic acid (a long-chain fatty acid) is consistent with recent microarray studies identifying altered lipid metabolism genes, while alterations in Arginine and Proline metabolism are consistent with recent studies identifying elevated L-arginine in DMD patient sera as a biomarker of disease (alterations in DMD or GRMD muscle itself have not previously been reported).Together, these studies demonstrate muscle-specific alterations in GRMD-affected muscle, which illustrate previously unidentified metabolic changes.
University of North Carolina at Chapel Hill
DepartmentMcAllister heart Institute, Department of Internal medicine, Department of Pathology & Laboratory, Department of Pharmacology
LaboratoryMultiple Centers
Last NameWillis
First NameMonte
Address111 Mason Farm Road, MBRB 2336, Chapel Hill, North Carolina, 27599-7126, USA
Phone(984) 999-5431
Submit Date2017-04-27
Study CommentsSkeletal Muscle (Biceps femoris (BF), long digital extensor(LDE))
Raw Data AvailableYes
Raw Data File Type(s)d
Analysis Type DetailGC-MS
Release Date2017-11-20
Release Version1
Monte Willis Monte Willis application/zip

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Sample Preparation:

Sampleprep ID:SP001175
Sampleprep Summary:The samples were crash deprotonized by methanol precipitation and spiked with D27-deuterated myristic acid (D27-C14:0) as an internal standard for retention-time locking and dried. The trimethylsilyl-D27-C14:0 standard retention time (RT) was set at 16.727 min. Reactive carbonyls were stabilized at 50C with methoxyamine hydrochloride in dry pyridine. Metabolites were made volatile with TMS groups using N-methyl-N-(trimethylsilyl) trifluoroacetamide or MSTFA with catalytic trimethylchlorosilane at 50C.