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The functional relationship between the two subcellular compartments involved in catabolism of triglycerides, i.e. lysosomes and lipid-containing cytoplasmic vacuoles, has been investigated using cultured fibroblasts from patients affected with two different genetic lipid (triacylglycerol) storage disorders: Wolman disease and multisystemic lipid storage myopathy. As shown by metabolic studies in intact cultured cells, lysosomal degradation of exogenous labelled triacylglycerols (incorporated into lipoproteins and internalized via the apo B/E receptor pathway) was blocked in Wolman cells, whereas catabolism of endogenously biosynthesized triacylglycerols was in the normal range. In contrast, in fibroblasts from multisystemic lipid storage myopathy, the degradation of endogenous triacylglycerols was blocked, whereas that of exogenous triacylglycerols (i.e. from lipoproteins) was normal. This comparative study demonstrates that the lysosomal and cytoplasmic compartments are functionally independent. Enzymatic studies allow one to discriminate clearly between 3 lipases and 2 carboxylesterases the role of which is discussed.

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Epstein-Barr virus (EBV) transformed lymphoid cell lines (LCL) were established from blood lymphocytes of a patient affected with Wolman's disease (WD) and from her parents. These LCL showed a severe deficiency in acid lipase activity using every substrate in comparison to LCL from normal subjects, in which acid lipase activity was similar to that in blood lymphocytes. In the LCL from Wolman's disease a major accumulation of neutral lipids was observed, mainly cholesteryl esters, CE (amount around 7 times higher than in normal cells and ratio of esterified/free cholesterol increased by 10 times) and to a lesser extent triglycerides, TG (amount increased by 1.5 times). Electron microscopy showed the storage vacuoles of neutral lipids quite characteristic of this lysosomal disease. The reported data demonstrated the validity of transformed LCL as a cellular model system in culture for experimental studies of Wolman's disease and for investigating the lysosomal metabolism of neutral lipids.