EVIDENCE FOR LIPASE ABNORMALITY - HIGH-LEVELS OF FREE AND TRIACYLGLYCEROL FORMS OF UNSATURATED FATTY-ACIDS IN NEURONAL CEROID-LIPOFUSCINOSIS TISSUE

Total lipid obtained from normal and different forms of neuronal ceroid-lipofuscinoses (NCL) tissues was analyzed by high performance thin layer chromatography (HPTLC). We observed a large (> 6-fold) increase in a lipid band corresponding to triolein for NCL dog pancreas and spleen and juvenile human NCL brain and infantile NCL spleen. The accumulation was less pronounced for the brain samples but apart from increased dolicholmonophosphate levels, other lipids appeared normal. Normal dog, goat, or human spleen contained virtually no triacylglycerol, and of the pathological controls, beta-mannosidosis goat spleen showed no triacylglycerol band at all. A sample of human spleen from a patient with lymphoma-associated splenomegaly displayed a strong triacylglycerol band, but gas chromatography-mass spectrometry (GC/MS) of the bands showed an equal increase in both saturated and unsaturated fatty acid containing triacylglycerols in the splenomegaly sample, in keeping with the notion of non-specific fat deposition in damaged tissue. In contrast, in all the NCL samples (spleen, pancreas, and brain) a prominent increase in the proportion of unsaturated fatty acids was observed in both free fatty acid and/or triacylglycerol bands following GC/MS. The NCL-English setter dog pancreas showed a major presence of oleic acid (18:1) (twofold increase) as compared to normal, while dog and infantile human NCL spleen samples and juvenile Batten brain (human) displayed a robust increase in linoleic acid (18:2) and sometimes in oleic acid and arachidonic acid (20:4) (for infantile human NCL spleen). For the infantile human NCL spleen sample an increase in linoleic acid in both free fatty acid (3.2-fold) and triacylglycerol (10-fold) was observed. This suggests a new mechanism by which polyunsaturated fatty acids can be transported to various parts of an NCL-affected mammalian body in packages such as triacylglycerol and/or serum albumin:free fatty acid complex. Such polyunsaturated fatty acids could eventually lead to the ceroid-lipofuscin pigment characteristic of NCl tissues through peroxidation to aldehyde with subsequent Schiff base formation. This could possibly explain the deposition of ceroid-lipofuscin in widely different and non-proximal tissues such as the pancreas and the brain.