|SHEN, LI-RONG - Massachusetts General Hospital|
|Lai, Chao Qiang|
|FENG, XIANG - Massachusetts General Hospital|
|WANG, JING-DONG - Massachusetts General Hospital|
|LI, DUO - Zhejiang University|
|ORDOVAS, JOSE - Jean Mayer Human Nutrition Research Center On Aging At Tufts University|
|KANG, JING-XUAN - Massachusetts General Hospital|
Submitted to: Journal of Lipid Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/23/2010
Publication Date: 10/1/2010
Citation: Shen, L., Lai, C., Feng, X., Parnell, L.D., Wang, J., Li, D., Ordovas, J.M., Kang, J. 2010. Drosophila lacks C20 and C22 polyunsaturated fatty acids. Journal of Lipid Research. 51(10)2985-2992.
Interpretive Summary: The fruit fly Drosophila melanogaster has long been considered an ideal model organism to investigate a wide range of biological processes. The intersection of nutrition and genome, termed nutrigenomics, however, presents a new area of research for which the role of Drosophila has yet to be fully illustrated. This is especially true for the processes of the breakdown of fatty acids. The primary objective of this study was to examine the breakdown of polyunsaturated fatty acids (PUFAs) with carbon-chain lengths of 20 and 22 in Drosophila. Four distinct Drosophila stocks or sub-types were fed diets supplemented with six different types of PUFAs at 50 mg/100g base diet and fatty acid compositions of three developmental stages were measured using a standard, highly sensitive gas chromatography method. Analysis showed that flies fed only a base diet not supplemented with any of the six PUFAs do not produce any detectable levels of PUFAs of carbon-chain lengths of 20 or 22 in larvae, pupae or adults. This result held for flies fed a diet augmented with the 20-carbon omega-6 PUFA arachidonic acid or with the 18-carbon omega-3 PUFA alpha linolenic acid, both of which are common in the human diet and act as building blocks for longer chain PUFAs. When the fly diet was supplemented with the 22-carbon omega-3 docosahexaenoic acid or DHA, the DHA was reduced to 20-carbon omega-3 eicosapentaenoic acid or EPA. When the fly diet was supplemented with the 22-carbon omega-6 docosatetraenoic acid or DTA, the DTA was reduced to 20-carbon omega-6 arachidonic acid. No other PUFA of carbon-chain length 20, besides arachidonic acid and EPA was observed. These results substantiate our bioinformatics analysis that D. melanogaster lacks a gene encoding delta-5/delta-6 desaturase activity, an activity necessary for the regulation of unsaturation of fatty acids via the introduction of double bonds between defined carbons of the fatty acyl chain. Together, these findings demonstrate that D. melanogaster lacks PUFAs of carbon-chain lengths of 20 and 22, whereas longer-chained PUFAs are broken down into shorter chain fatty acids. In conclusion, these results suggest that there is a fundamental difference between the biochemical processes of PUFAs between D. melanogaster and H. sapiens, thus limiting its use as a model for the study of lipids in humans.
Technical Abstract: Drosophila melanogaster has been considered an ideal model organism to investigate human diseases and genetic pathways. Whether Drosophila is an ideal model for nutrigenomics, especially for fatty acid metabolism, however, remains to be illustrated. This study was to examine the metabolism of C20 and C22 polyunsaturated fatty acids (PUFAs) in Drosophila. Four Drosophila stocks were fed diets supplemented with six types of PUFAs: 18:2n-6, 18:3n-3, 20:5n-3, 22:6n-3, 22:4n-6 and 20:4n-6 at 50 mg/100g base diet. Fatty acid compositions of three developmental stages were measured using a standard gas chromatography method. The predominant fatty acids in adults fed the base diet were 14:0 (16.67%), 16:0 (16.11), 16:1n-7 (21.81), 18:1n-9 (20.03) and 18:2n-6 (14.01). No C20 or C22 PUFAs were detected in larvae, pupae and adults fed the base diet, nor in flies supplemented with LA and ALA. In the DHA-supplemented group, the 22C PUFA was reduced to EPA. In the DTA dietary group, the 22C PUFA was reduced to AA. No other C20 and C22 PUFAs were detected except AA and EPA when the diet contained those PUFAs. These findings, coupled with a sequence scan of the fly genome indicating that no gene encoding delta-5/delta-6 desaturase is present, indicate that Drosophila lacks C20 and C22 PUFAs, whereas the long chain of DHA and DTA are metabolized to shorter chain fatty acids in Drosophila. This suggests that Drosophila possesses a lipid metabolism and gene set distinct from mammals, and thus has limited value as a model for the study of lipid metabolism in humans.