Cholesterol alterations in young dystrophic mice

Abstract

Cholesterol and cholesteryl ester concentrations and cholesteryl ester fatty acid substituents have been measured during the first 10 weeks of life in tissues of normal and dystrophic mice. In normal Swiss and 129ReJ(+/?) mice the concentrations of both cholesterol and cholesteryl esters remain essentially constant in liver, increase in brain and fall sharply in both thigh (mixed fiber type muscles) and chest muscles (predominantly slow oxidative muscles) over this period. In all cases the concentration of free cholesterol exceeds that of esterified cholesterol. In dystrophic mice, similar patterns are found in brain and liver. In both thigh and chest muscles, however, the developmental pattern is significantly different. After an initial decrease the concentrations of cholesterol and cholesteryl esters increase rapidly with the largest increase occurring in the concentration of cholesteryl esters which by 10 weeks of age exceeds the concentration of cholesterol in chest muscle. During the same period the pattern of esterified fatty acids changes gradually in dystrophic tissues towards an increasing ratio of unsaturated/saturated fatty acids. By 10 weeks of age this ratio is significantly higher in dystrophic tissues than normal in all tissues tested.

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

“…3), whereas DMD-affected sections exhibited similar or higher intensities for cholesterol signal than for vitamin E (data not shown). This is also consistent with previous findings on dystrophic muscles (50)(51)(52). Therefore, Cholesterol, PC, and SM colocalization, associated with a much higher proportion of cholesterol, might suggest a tentative regulation and/or regeneration behavior of these highly damaged regions in human DMD-affected muscles.…”

Increased nonHDL cholesterol levels cause muscle wasting and ambulatory dysfunction in the mouse model of LGMD2B

“…In contrast, no significant relationship to TG levels was observed, suggesting that nonHDLc plays the major role in muscle pathology exacerbation in our model. Because Dysf is known to interact with anionic phospholipids and facilitate sarcolemma repair, it is possible that cholesterol-and lipid-rich environments may have unexpected effects on blunted sarcolemmal repair processes found in Dysf-deficient myofibers (26)(27)(28)(29). Cholesterol has been shown to be a key player in exocytosis and vesicle trafficking, where addition or depletion of cholesterol from the plasma membrane lead to dysregulated Ca 2+ -triggered vesicle fusion (27).…”