Muscle Lipids in Duchenne Muscular Dystrophy

Abstract

Summary The lipids of muscle and adipose tissue from normal males and of muscle from males with Duchenne muscular dystrophy were investigated. Triglyceride, the major neutral lipid, showed similar fatty acid compositions in all tissues examined. When the phospholipids of dystrophic muscle and of normal adipose tissue were compared with those of normal muscle, it was found that there was an increase in the proportion of sphingomyelin in dystrophic muscle, while adipose tissue had higher proportions of sphingomyelin and lysophosphatidylcholine but lower choline phosphoglyceride. In dystrophic muscle only small alterations from normal were observed in the fatty acid compositions of the individual phospholipids, whereas the phospholipids of adipose tissue had quite distinctive fatty acid compositions. An atrophic muscle sample resulting from poliomyelitis consisted almost entirely of connective tissue and fat and had a phospholipid composition similar to that of adipose tissue. From a comparison of the results for all the types of tissue studied, it is evident that the increase in sphingomyelin in dystrophic muscle biopsies and the changes in the fatty acid compositions of individual phospholipids may be accounted for by the increased amounts of fat and connective tissue which are present in dystrophic muscle samples. In a case each of polymyositis, limb girdle muscular dystrophy and an autosomal recessive form of muscular dystrophy, the results obtained for the phospholipid composition of the muscle sample were also normal or consistent with some contamination from fat and connective tissue.

Lipid mapping in human dystrophic muscle by cluster-time-of-flight secondary ion mass spectrometry imaging

“…Similar to the destructured (regenerating) zone in the mdx mouse model, these ratio values were ,1.This could denote an intensive regenerating activity and not degeneration, as would be expected from the color, aspect, and absence of fascicles on the microscope image of spot 3. Additionally, compared with spot 2, the lower R 1 produced by the cells of spot 3 indicates that Lipid mapping with cluster-ToF-SIMSthese cell PCs have incorporated less C18:2, as observed previously in DMD-affected human muscles (21,22). This also means that spot 2 is in a more stable state than spot 3 and confirms the pseudohealthy nature of spot 2.…”

“…As mentioned previously, this is probably attributable to the significantly low amount of destructured fibers and adipose and connective tissues in the dystrophic mouse muscle (1). Similarly, a lower incorporation of C18:2 in PCs has been observed in human dystrophic muscles, compared with healthy muscles, together with increased levels of C18:1 and C18:0 (21,22). The variation of fatty acid composition between the different areas revealed in the present study can be interpreted as an attempt to stabilize the dystrophic cells, because the incorporation of saturated fatty acids in cell wall phospholipids reduces membrane flexibility.…”

“…However, the poor contrast of the ToF-SIMS images of intact PCs did not provide spatial information; thus, the composition modification revealed by MALDIToF could not be confirmed. Earlier studies (21,22) have also shown that membrane PCs of the human dystrophic muscle incorporated less C18:2 fatty acyl chains than the healthy muscle, but more C18:1 and C18:0.…”

“…Ceramides (SM derivatives) are vital signaling substances for tumors, forming SM-rich vesicles, and are responsible for their proliferation and survival (43). Additionally, it has been shown that phospholipase C activity increases in dystrophic mouse muscle, together with an increase of SM and TGs (21,44,45). This enzyme converts PC species into DGs and phosphocholine, both precursors of SM and TG biosynthesis (46,47).…”

Delineating the role of alterations in lipid metabolism to the pathogenesis of inherited skeletal and cardiac muscle disorders

“…Additionally, the phospholipid-to-TG ratio was decreased in DMD patients, indicating a perturbation in the lipid bilayer ( 104 ). An increase in the C18:1 fatty acid (oleate) in PC of human dystrophic muscle was associated with a decrease in C18:2 fatty acid (linoleate) ( 7,100 ). In biopsies of rectus abdominus and gastrocnemius muscle in 3-to 5-year-old males diagnosed with DMD, an increase in SM and cholesterol content was coupled with a decrease in PC and choline plasmalogen ( 105 ).…”