Diagnostics and therapy

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There are several studies indicating the potential of MS-lipidomics in the diagnosis of genetic and other diseases. Perhaps the most prominent example is the diagnosis of the Barth syndrome based on the analysis of the phospholipid species of the platelets. Platelets from patients with this disorder contained greatly reduced levels of the CL molecular species containing four linoleyl (18:2) residues as compared to unaffected individuals [61]. LC-MS analysis allows the detection of this diagnostic parameter far more easily than traditional methods of lipid analysis, and potentially also allows one to monitor the therapeutic effects of fatty acid supplementation [60]. MS-lipidomics is also helpful in diagnosis and therapy of other hereditary diseases like Fabry disease based on increased levels of, e.g., trihexosyl and lactosylceramides found in the urine due to lack of the lysosomal a-galactosidase [130,131]. Also, some peroxisomal disorders like X-linked adrenoleykodystrophy and Zellweger syndrome could be diagnosed based on MS analysis of long-chain fatty acids [132], ceramides [133], or PE plasmalogens (our unpublished data). MS-lipidomics may also allow one to diagnose the Lowe syndrome based on altered polyphosphoinositol lipid composition [65]. MS analysis of ascitic fluid from patients with ovarian cancer has revealed increased levels of some lysophospholipids, which could thus provide useful biomarkers for this disease [134,135]. Yet, MS-lipidomics has significant potential in diagnosing and judging the predisposition for various multifactorial disorders, such as type 2 diabetes and artherosclerosis, particularly when combined with the analysis of other biomarkers [136].

7.2. Disease mechanisms

MS-lipidomics is also likely to be very helpful in resolving the metabolic defects underlying various common diseases, like type 2 diabetes, atherosclerosis, Alzheimer's disease, and different cancers. So far, MS-lipidomics has been helpful in understanding the mechanism of lipid accumulation in atherosclerotic plaques [137,138], optic nerve hypoplasia [139], cystic fibrosis [140], neuronal-ceroid lipofuscinosis [18], aggressive periodontal tissue damage [141], ulcerative colitis [142], glycosphingolipid disorders [143], and diabetic cardiomyopathy [144].

Besides compositional data, MS is also highly useful to study lipid metabolism in cells or whole animals. A variety of heavy isotope (2H, 13C)-labeled lipid precursors are commercially available and can be used to obtain highly detailed data regarding the biosynthetic routes and kinetics of lipid metabolism. So far this approach has been employed to study, e.g., the contribution of different pathways to the biosynthesis of PC in malignant cells [25], ^-oxidation of fatty acids in peroxisomal disorders [145], surfactant PC synthesis [146], and lipid metabolism related to obesity [147].

7.3. Nutrition and other issues

MS-lipidomics also offers a powerful tool for nutritional studies. For instance, the effect of caloric restriction on lipid composition of murine myocardium has been investigated by this method [148]. In another study, the effect of structure of TAGs on the chylomicron TAG composition in humans was investigated [149]. MS-lipidomics also appears to be useful in resolving the mechanisms underlying drug addiction and related issues [150].

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