Department of Physiology and Functional Genomics, University of Florida, Gainesville, FL, USA.
Department of Biochemistry and Molecular Biology, Southeast Center for Integrated Metabolomics, University of Florida, Gainesville, FL, USA.
NMR Biomed. 2019 May;32(5):e4075. doi: 10.1002/nbm.4075. Epub 2019 Mar 8.
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 H MRI/MRS, in isolated muscles using H-HR-MAS NMR, and in serum using high resolution H/ 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 , 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.
杜氏肌营养不良症（DMD）是一种致命的 X 连锁遗传性疾病。在 DMD 中，肌营养不良蛋白的缺失导致肌细胞膜完整性降低，导致肌肉逐渐被纤维脂肪组织取代。缺乏肌营养不良蛋白对肌肉和全身代谢的影响尚不清楚。因此，为了确定肌营养不良蛋白缺失对代谢的影响，我们在 mdx 小鼠的肌肉损伤和稳定的两个不同阶段研究了代谢和脂质谱。我们在 6 周和 24 周龄的 mdx 小鼠的血清和肌肉中测量了 NMR 可检测的代谢物和脂质谱。使用 H MRI/MRS 在肌肉中进行了体内代谢物的测定，使用 H-HR-MAS NMR 在分离的肌肉中进行了测定，在血清中使用高分辨率 H/ C NMR 进行了测定。与对照小鼠相比，营养不良小鼠具有独特的脂质饱和度谱，显示出与年龄相关的代谢变化。在 6 周龄的 mdx 小鼠中，血清脂质增加，脂质饱和度在 6 至 24 周之间发生变化。血清牛磺酸-肌酸比在 mdx 的整个生命周期中增加，但在对照小鼠中没有增加。此外，血清中脂质的饱和度指数随时间增加，但组织中脂质的饱和度指数随时间降低。最后，我们证明了 MRI-T 与组织和血清脂质谱之间存在相关性，MRI-T 是炎症/水肿的一个强有力指标。这些结果表明，在营养不良肌肉中反复发生的肌肉损伤和再生过程中，组织和血清中的代谢物存在复杂的时间变化。
