Abnormal lipid metabolism in skeletal muscle tissue of patients with muscular dystrophy: In vitro, high-resolution NMR spectroscopy based observation in early phase of the disease

Srivastava, Niraj Kumar; Yadav, Rashmi; Mukherjee, Somnath; Pal, Lily; Sinha, Neeraj

doi:10.1016/j.mri.2017.01.001

Cited by 37 publications

(43 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Others have shown that lipid composition in the muscle and blood of patients with DMD is altered . Following repeated bouts of muscle damage, the contractile tissue of the muscle is replaced by fibrofatty tissue . We found that the ui increased but the pi decreased in 6‐week‐old mdx mice compared with controls.…”

Section: Discussionmentioning

confidence: 50%

“…Linoleic acid was higher in controls than in mdx mice. In DMD muscle, it has been recently shown by Srivastava et al that linoleic acids are significantly reduced in DMD muscle compared with normal/control individuals. Alterations in polyunsaturated fatty acids in erythrocytes from DMD patients have also been reported.…”

Section: Discussionmentioning

confidence: 97%

“…Many studies have investigated the changes of metabolism secondary to the loss of dystrophin . When dystrophin is not functional, there are significant alterations in nitric oxide synthesis, energy metabolism, and lipid synthesis .…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Age‐dependent changes in metabolite profile and lipid saturation in dystrophic mice

et al. 2019

View full text Add to dashboard Cite

Duchenne Muscular Dystrophy (DMD) is a fatal X-linked genetic disorder. In DMD, the absence of the dystrophin protein causes decreased sarcolemmal integrity resulting in progressive replacement of muscle with fibrofatty tissue. The effects of lacking dystrophin on muscle and systemic metabolism are still unclear. Therefore, to determine the impact of the absence of dystrophin on metabolism, we investigated the metabolic and lipid profile at two different, well-defined stages of muscle damage and stabilization in mdx mice. We measured NMR-detectable metabolite and lipid profiles in the serum and muscles of mdx mice at 6 and 24 weeks of age. Metabolites were determined in muscle in vivo using 1 H MRI/MRS, in isolated muscles using 1 H-HR-MAS NMR, and in serum using high resolution 1 H/ 13 C NMR. Dystrophic mice were found to have a unique lipid saturation profile compared with control mice, revealing an age-related metabolic change. In the 6-week-old mdx mice, serum lipids were increased and the degree of lipid saturation changed between 6 and 24 weeks.The serum taurine-creatine ratio increased over the life span of mdx, but not in control mice. Furthermore, the saturation index of lipids increased in the serum but decreased in the tissue over time. Finally, we demonstrated associations between MRI-T 2 , a strong indicator of inflammation/edema, with tissue and serum lipid profiles. These results indicate the complex temporal changes of metabolites in the tissue and serum during repetitive bouts of muscle damage and regeneration that occur in dystrophic muscle.

show abstract

Section: Discussionmentioning

confidence: 50%

Section: Discussionmentioning

confidence: 97%

See 1 more Smart Citation

Age‐dependent changes in metabolite profile and lipid saturation in dystrophic mice

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Much of the previous work that has explored metabolic alterations that occur in DMD animal models has focused on cardiac muscle (13), but some studies have been performed in skeletal muscle tissue. Limited studies in human subjects have also demonstrated reduced succinate and branched chain amino acids, increased glucose, triglycerides and cholesterol, and no difference in creatine/phosphocreatine or phospholipids in muscle biopsies in patients with DMD compared to controls (42,43). The muscles from golden retriever canines with a form of muscular dystrophy demonstrate reduced Krebs cycle intermediates compared to wild type animals (1) and similar reductions in oxidative capacity were also observed in the muscles of mdx mice (11).…”

Section: Metabolomics and Lipidomicsmentioning

confidence: 99%

Multiomics Analysis of the mdx/mTR Mouse Model of Duchenne Muscular Dystrophy

Pelt

Kharaz

Sarver

et al. 2019

Preprint

View full text Add to dashboard Cite

Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disease characterized by extensive muscle weakness. Patients with DMD lack a functional dystrophin protein, which transmits force and organizes the cytoskeleton of skeletal muscle. Multiomic studies evaluate combined changes in the transcriptome, proteome, and metabolome, and have been proposed as a way to obtain novel insight about disease processes from preclinical models.We therefore sought to use this approach to study pathological changes in dystrophic muscles.We evaluated hindlimb muscles of male mdx/mTR mice, which lack a functional dystrophin protein and have deficits in satellite cell abundance and proliferative capacity. Wild type (WT) C57BL/6J mice served as controls. Muscle fiber contractility was measured, along with changes in the transcriptome using RNA sequencing, and in the proteome, metabolome, and lipidome using mass spectroscopy. While mdx/mTR mice displayed gross pathological changes and continued cycles of degeneration and regeneration, we found no differences in fiber contractility between strains. However, there were numerous changes in the transcriptome and proteome related to protein balance, contractile elements, extracellular matrix, and metabolism. There was only a 53% agreement in fold change data between the proteome and transcriptome, highlighting the need to study protein abundance along with gene expression measures. Numerous changes in markers of skeletal muscle metabolism were observed, with dystrophic muscles exhibiting elevated glycolytic metabolites. These findings highlight the utility of multiomics in studying muscle disease, and provide additional insight into the pathological changes in dystrophic muscles that might help to guide evidence-based exercise prescription in DMD patients.

show abstract

“…Pathologic defects in muscle trimethylamine compounds-to-creatine ratio were found in facioscapulohumeral muscular dystrophy already prior to macroscopic muscle fat infiltration [171]. Furthermore, analytic in vitro MRS could detect alteration of lipid metabolism in patients with muscular dystrophy in early phase of the disease [172].…”

Section: Skeletal Muscle Myopathiesmentioning

confidence: 99%

Multinuclear Magnetic Resonance Spectroscopy of Human Skeletal Muscle Metabolism in Training and Disease

Valkovič¹,

Klepochová²,

Krššák³

2018

Muscle Cell and Tissue - Current Status of Research Field

View full text Add to dashboard Cite

In this chapter, techniques and application of multinuclear (1 H, 13 C, and 31 P) in vivo magnetic resonance spectroscopy (MRS) for the assessment of skeletal muscle metabolism in health and disease are described. Studies focusing on glucose transport and utilization, lipid storage and consumption, handling of energy rich phosphates, and measurements of newly emerging noninvasive biomarkers, i.e., acetylcarnitine and carnosine are summarized. Muscle metabolism connections to exercise physiology and the development as well as possible treatment of metabolic diseases, such as obesity and diabetes are also discussed. Taken together, multinuclear in vivo MRS on humans helped to uncover defects in skeletal muscle metabolic pathways in insulin-resistant conditions; and to discover links between defects in mitochondrial activity/capacity and lipid metabolism, as well as defects in whole-body and/or muscle glucose metabolism. There is also to mention that several of the MR-derived readouts are affected by both training status and metabolic disease in a specific way, and thus could serve as potential markers of training status and metabolic flexibility.

show abstract

Abnormal lipid metabolism in skeletal muscle tissue of patients with muscular dystrophy: In vitro, high-resolution NMR spectroscopy based observation in early phase of the disease

Cited by 37 publications

References 49 publications

Age‐dependent changes in metabolite profile and lipid saturation in dystrophic mice

Age‐dependent changes in metabolite profile and lipid saturation in dystrophic mice

Multiomics Analysis of the mdx/mTR Mouse Model of Duchenne Muscular Dystrophy

Multinuclear Magnetic Resonance Spectroscopy of Human Skeletal Muscle Metabolism in Training and Disease

Contact Info

Product

Resources

About