Original Article

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

Correspondence to: Rosalind A. Coleman.

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.—Igal, R. A., and R. A. Coleman. Neutral lipid storage disease: a genetic disorder with abnormalities in the regulation of phospholipid metabolism. J. Lipid Res. 1998. 39: 31–43.

Supplementary key words: triacsin C, neutral lipid storage disease, phospholipid synthesis, lipid droplets, glycerolipids

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				P. M. Elias, M. L. Williams, W. M. Holleran, Y. J. Jiang, and M. Schmuth Thematic review series: Skin Lipids. Pathogenesis of permeability barrier abnormalities in the ichthyoses: inherited disorders of lipid metabolism J. Lipid Res., April 1, 2008; 49(4): 697 - 714. [Abstract] [Full Text] [PDF]

				D. L. Brasaemle Thematic review series: Adipocyte Biology. The perilipin family of structural lipid droplet proteins: stabilization of lipid droplets and control of lipolysis J. Lipid Res., December 1, 2007; 48(12): 2547 - 2559. [Abstract] [Full Text] [PDF]

				J. M. Brown, S. Chung, A. Das, G. S. Shelness, L. L. Rudel, and L. Yu CGI-58 facilitates the mobilization of cytoplasmic triglyceride for lipoprotein secretion in hepatoma cells J. Lipid Res., October 1, 2007; 48(10): 2295 - 2305. [Abstract] [Full Text] [PDF]

				M. Schweiger, R. Schreiber, G. Haemmerle, A. Lass, C. Fledelius, P. Jacobsen, H. Tornqvist, R. Zechner, and R. Zimmermann Adipose Triglyceride Lipase and Hormone-sensitive Lipase Are the Major Enzymes in Adipose Tissue Triacylglycerol Catabolism J. Biol. Chem., December 29, 2006; 281(52): 40236 - 40241. [Abstract] [Full Text] [PDF]

				P. Liu, Y. Ying, Y. Zhao, D. I. Mundy, M. Zhu, and R. G. W. Anderson Chinese Hamster Ovary K2 Cell Lipid Droplets Appear to Be Metabolic Organelles Involved in Membrane Traffic J. Biol. Chem., January 30, 2004; 279(5): 3787 - 3792. [Abstract] [Full Text] [PDF]

				R. A. Igal, J. M. Caviglia, I. N. T. de Gómez Dumm, and R. A. Coleman Diacylglycerol generated in CHO cell plasma membrane by phospholipase C is used for triacylglycerol synthesis J. Lipid Res., January 1, 2001; 42(1): 88 - 95. [Abstract] [Full Text]