title: Towards a whole-body systems [multi-organ] lipidomics in Alzheimer's disease.
abstract: Preclinical and clinical evidence suggests that docosahexaenoic acid (DHA), an omega-3 fatty acid derived from diet or synthesized in the liver, decreases the risk of developing Alzheimer's disease (AD). DHA levels are reduced in the brain of subjects with AD, but it is still unclear whether human dementias are associated with dysregulations of DHA metabolism. A systems biological view of omega-3 fatty acid metabolism offered unexpected insights on the regulation of DHA homeostasis in AD [1]. Results of multi-organ lipidomic analyses were integrated with clinical and gene-expression data sets to develop testable hypotheses on the functional significance of lipid abnormalities observed and on their possible mechanistic bases. One surprising outcome of this integrative approach was the discovery that the liver of AD patients has a limited capacity to convert shorter chain omega-3 fatty acids into DHA due to a deficit in the peroxisomal d-bifunctional protein. This deficit may contribute to the decrease in brain DHA levels and contribute to cognitive impairment.
authors.affiliation: Department of Pharmacology, 3101 Gillespie NRF, University of California, Irvine, CA 92697-4625, USA.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Astarita
authors.forename: Daniele
authors.initials: D
authors.lastname: Piomelli
mesh_terms: D015067:17-Hydroxysteroid Dehydrogenases / Q000235:genetics / Q000378:metabolism*; D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism*; D004281:Docosahexaenoic Acids / Q000378:metabolism*; D006801:Humans; D006836:Hydro-Lyases / Q000235:genetics / Q000378:metabolism*; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism*; D009928:Organ Specificity / Q000235:genetics; D064029:Peroxisomal Multifunctional Protein-2; D020675:Peroxisomes / Q000235:genetics / Q000378:metabolism*
chemical_list: D004281:Docosahexaenoic Acids; D015067:17-Hydroxysteroid Dehydrogenases; D006836:Hydro-Lyases; D064029:Peroxisomal Multifunctional Protein-2; C104587:HSD17B4 protein, human