Drosophila lacks C20 and C22 PUFAs

Drosophila melanogaster has been considered a model organism for investigating human diseases and genetic pathways. Whether Drosophila is an ideal model for nutrigenomics, especially for FA metabolism, however, remains to be illustrated. The aim of this study was to examine the metabolism of C20 and C22 PUFAs in Drosophila. Analysis of FA composition revealed a complete lack of C20 and C22 PUFAs in the body tissue of larvae, pupae, and adult flies fed either a base or supplemented diet abundant in the PUFA precursors linoleic acid and α-linolenic acid. PUFA with >C20 could only be found in flies supplemented with specific FAs. Interestingly, the supplemented C22 PUFAs docosahexaenoic acid (22:6n-3) and docosatetraenoic acid (22:4n-6) were largely converted to the shorter chain C20 PUFAs eicosapentaenoic acid (20:5n-3) and arachidonic acid (20:4n-6), respectively. Furthermore, a genome sequence scan indicated that no gene encoding Δ-6/ Δ-5 desaturases, the key enzymes for the synthesis of C20/C22 PUFA, was present in Drosophila. These findings demonstrate that Drosophila lacks the capability to synthesize the biologically important C20 and C22 PUFAs, and thereby argue that Drosophila is not a valid model for the study of lipid metabolism and related diseases. Drosophila melanogaster has been considered a model organism for investigating human diseases and genetic pathways. Whether Drosophila is an ideal model for nutrigenomics, especially for FA metabolism, however, remains to be illustrated. The aim of this study was to examine the metabolism of C20 and C22 PUFAs in Drosophila. Analysis of FA composition revealed a complete lack of C20 and C22 PUFAs in the body tissue of larvae, pupae, and adult flies fed either a base or supplemented diet abundant in the PUFA precursors linoleic acid and α-linolenic acid. PUFA with >C20 could only be found in flies supplemented with specific FAs. Interestingly, the supplemented C22 PUFAs docosahexaenoic acid (22:6n-3) and docosatetraenoic acid (22:4n-6) were largely converted to the shorter chain C20 PUFAs eicosapentaenoic acid (20:5n-3) and arachidonic acid (20:4n-6), respectively. Furthermore, a genome sequence scan indicated that no gene encoding Δ-6/ Δ-5 desaturases, the key enzymes for the synthesis of C20/C22 PUFA, was present in Drosophila. These findings demonstrate that Drosophila lacks the capability to synthesize the biologically important C20 and C22 PUFAs, and thereby argue that Drosophila is not a valid model for the study of lipid metabolism and related diseases. The fruit fly Drosophila melanogaster is one of the most intensively studied organisms in biology and serves as a model system for the investigation of many developmental and cellular processes common to more-complex eukaryotes, including humans (1Adams M.D. Celniker S.E. Holt R.A. Evans C.A. Gocayne J.D. Amanatides P.G. Scherer S.E. Li P.W. Hoskins R.A. Galle R.F. The genome sequence of Drosophila melanogaster.Science. 2000; 287: 2185-2195Crossref PubMed Scopus (4744) Google Scholar). Drosophila distinguishes itself from yeast (Saccharomyces cerevisiae) and nematodes (Caenorhabditis elegans) with its adipose-like tissues and a lipid transport system, making it a closer model to humans. Drosophila has been considered an ideal model since around 1915, when it was first used to study aging (2Helfand S.L. Rogina B. Molecular genetics of aging in the fly: is this the end of the beginning?.Bioessays. 2003; 25: 134-141Crossref PubMed Scopus (53) Google Scholar, 3Piper M.D. Skorupa D. Partridge L. Diet, metabolism and lifespan in Drosophila.Exp. Gerontol. 2005; 40: 857-862Crossref PubMed Scopus (80) Google Scholar). Since the complete genomic sequence of the fly was released in early 2000, 177 out of 289 (∼61%) of the human genes responsible for disease have been found to have strong homologs or orthologs in the fly (4Ruden D.M. Lu X. Evolutionary conservation of metabolism explains how Drosophila nutrigenomics can help us understand human nutrigenomics.Genes Nutr. 2006; 1: 75-83Crossref PubMed Google Scholar). Two-thirds of genes implicated in human cancers also have a counterpart in the fly genome. Furthermore, the use of Drosophila as a model has many advantages, including its sophisticated genetics, small genome size, high fecundity, low cost, and short generation time (4Ruden D.M. Lu X. Evolutionary conservation of metabolism explains how Drosophila nutrigenomics can help us understand human nutrigenomics.Genes Nutr. 2006; 1: 75-83Crossref PubMed Google Scholar). Candidate pathways influenced by nutrients can be identified first in Drosophila, and later verified in mouse models and humans. Drosophila is thus currently used as a model organism to study human diseases, including obesity, diabetes, cancer, cardiovascular disease, age-related diseases, and longevity. Lipids come in a wide variety and have many functions in cells besides simply being used for energy. Not only do they make up cell membranes, but they and their products serve as intra- and extracellular messengers that control and regulate many vital bodily functions. Imbalances of lipids cause or play a role in diseases that affect millions worldwide, such as heart disease, cancer, diabetes, Alzheimer's, etc. Certain PUFAs are especially crucial components of human nutrition, including ω-6 (n-6) and ω-3 (n-3) FAs, which are essential nutrients and important determinants of the structure and function of mammalian cells (5Salem N.J. Simopoulos A.P. Galli C. Lagarde M. Knapp H.R. Fatty acids and lipids from cell biology to human disease.Lipids. 1996; 31: 1-326PubMed Google Scholar). In particular, the dietary essential FAs linoleic acid (LA,18:2n-6) and α-linolenic acid (ALA, 18:3n-3) are precursors for the important long-chain PUFAs arachidonic acid (AA, 20:4n-6), eicosapentaenoic acid (EPA, 20:5n-3), and docosahexaenoic acid (DHA, 22:6n-3), which are synthesized through a series of desaturation, catalyzed sequentially by