Neutral lipid storage disease: a genetic disorder with abnormalities in the regulation of phospholipid metabolism.

Neutral lipid storage disease (NLSD) is an autosomal recessive disorder characterized by the presence of numerous lipid droplets in virtually all tissues examined. The increased cellular triacylglycerol content results from defective recycling of triacylglycerol-derived diacylglycerol to phospholipids (Igal, R. A. and R. A. Coleman. 1996. J. Biol. Chem. 271: 16644-16651). In order to determine whether de novo glycerolipid synthesis is also altered in NLSD, we compared the ability of normal human skin fibroblasts and fibroblasts from a patient with NLSD to incorporate phospholipid precursors into cell lipids. NLSD cells had increased rates of incorporation of [14C]oleic acid and [3H]glycerol into triacylglycerol and all phospholipid species except phosphatidylethanolamine. However, the cell content of each phospholipid species was similar in control and NLSD cells, indicating a higher turnover rate in NLSD cells for phosphatidylcholine, phosphatidylinositol, phosphatidylserine, and sphingomyelin. Labeling with [14C]choline and [14C]ethanolamine confirmed the increase in the rate of phosphatidylcholine synthesis and the decreased rate of phosphatidylethanolamine synthesis through their respective CDP pathways. The activities of the major regulatory enzymes of triacylglycerol, phosphatidylcholine, and phosphatidylethanolamine biosynthesis were similar in control and NLSD cells. Taken as a whole, this study provides strong evidence for an underlying regulatory defect in NLSD that alters the rates of synthesis and degradation of the major cellular phospholipids.