DIETARY EFFECTS ON MEMBRANE LIPIDS

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DESCRIPTION (adapted from the applicant's abstract): The long-range goal of this proposal is to understand the role of membrane lipids in the formation and utilization of membrane organelles. Control male mice secrete lysosomal enzymes and multilamellar bodies from the renal proximal tubule cells into the urine. These bodies are enriched in phosphatidylcholine containing C22:6-n-3 fatty acid that must be derived from the diet. The secretion of multilamellar bodies and lysosomal enzymes is blocked in human Chediak-Higashi syndrome and in the beige mouse mutant. This led to a working hypothesis that this lipid plays some role in the secretory process leading to urinary excretions of these lysosomal materials. The specific aims of this proposal are to investigate the influence of dietary lipids (docosahexaenoic acid, C22:6n-3) on the formation of lysosomal-like multilamellar bodies in control and Chediak-Higashi CHS) mice. The investigator proposes to (i) Determine if n-3 fatty acid levels in the diet affect urinary secretion of lysosomal enzymes and multilamellar bodies in control male mice, and (ii) Determine if n-3 fatty acid levels in the diet affect the block to urinary secretion in beige mutant male mice.