Skip to main content

Advertisement

SpringerLink
Log in

Drosophila Fed ARA and EPA Yields Eicosanoids, 15S-Hydroxy-5Z,8Z, 11Z, 13E-Eicosatetraenoic Acid, and 15S-Hydroxy-5Z,8Z,11Z,13E,17Z-Eicosapentaenoic Acid

  • Original Article
  • Published:
Lipids

Abstract

Drosophila melanogaster has been a widely used as a model system for its powerful genetic tools. However, it remains to be illustrated if Drosophila can be used to examine the biochemical and physiological metabolism of eicosanoids. Thus, the analysis on the metabolism of C20 polyunsaturated fatty acids (PUFA) in Drosophila was implemented with high performance liquid chromatography tandem mass spectrometry (UPLC–MS/MS). Fatty acid (FA) analysis of the whole body, head, and thorax-abdomen in Drosophila showed C20 PUFA could only be found in Drosophila fed diets supplemented with eicosapentaenoic acid (EPA) and arachidonic acid (ARA), but not in Drosophila fed base diets. The C20 PUFA were found in abundance in the head. Drosophila fed ARA- and EPA-supplemented diets yielded 15S-hydroxy-5Z,8Z,11Z,13E-eicosatetraenoic acid [15(S)-HETE] and 15S-hydroxy-5Z,8Z,11Z,13E,17Z-eicosapentaenoic acid [15(S)-HEPE], respectively, while other sampled eicosanoids could not be detected. Similar results were obtained by incubating fly tissue supplemented with ARA or EPA. Furthermore, a genome sequence scan indicated that no gene encoding the key enzymes synthesizing eicosanoids were found in Drosophila. These findings demonstrate that Drosophila may possess a special lipid metabolic system, which is different from mammals.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Abbreviations

ALA:

α-Linolenic acid (18:3n-3)

ARA:

Arachidonic acid (20:4n-6)

ALOX5:

Arachidonate 5-lipoxygenase

ALOX12:

Arachidonate 12-lipoxygenase

ALOX15:

Arachidonate 15-lipoxygenase

ALOX15B:

Arachidonate 15-lipoxygenase B

BHT:

Butylhydroxytoluol

COX:

Cyclooxygenases

CYP:

Cytochrome P450

CYP2C8:

Cytochrome P450 2C8 isoform

CYP2C9:

Cytochrome P450 2C9

CYP4A11:

Cytochrome P450 4A11

CYP4F3:

Leukotriene-B(4) omega-hydroxylase 2 isoform a

CYP2J2:

Ytochrome P450 2J2

GC:

Gas chromatography

GSH:

Glutathione peroxidase

EET:

Epoxyeicosatrienoic acid

EPA:

Eicosapentaenoic acid (20:5n-3)

ESI:

Electrospray ionization

HETE:

Hydroxyeicosatetraenoic acid

HPETE:

Hydroperoxyeicosatetraenoic acid

HPLC–MS/MS:

High performance liquid chromatography tandem mass spectrometry

LA:

Linoleic acid (18:2n-6)

LC-MS:

Liquid chromatography–mass spectrometry

LOD:

Limit of detection

LOQ:

Limit of quantity

LOX:

Lipoxygenases

LT:

Leukotriene

LTB4 :

Leukotriene B4

MRM:

Multiple reactions monitoring

PG:

Prostaglandins

PGE3 :

Prostaglandin E3

PGH2 :

Prostaglandin H2

PGF3α :

Prostaglandin F3α

PLA2 :

Phospholipase A2

PUFA:

Polyunsaturated fatty acid

PGF2α :

Prostaglandin F2α

PGE2 :

Prostaglandin E2

PGE2-d4:

9-Oxo-11α,15S-dihydroxy-prosta-5Z,13E-Dien-1-oic-3,3,4,4-d4 acid

RSD:

Relative standard deviations

TX:

Thromboxane

5(S)-HpETE:

5S-Hydroperoxy-6E,8Z,11Z,14Z-eicosatetraenoic acid

11(12)-EET:

(±)11(12)-Epoxy-5Z,8Z,14Z-eicosatrienoic acid

15(S)-HEPE:

15S-Hydroxy-5Z,8Z,11Z,13E,17Z-eicosapentaenoic acid

15(S)-HETE:

15S-Hydroxy-5Z,8Z,11Z,13E-eicosatetraenoic acid

15(S)-HETE-d8 :

Techin

15(S)-HpEPE:

15S-Hydroperoxy-5Z,8Z,11Z,13E,17Z-eicosapentaenoic acid

15(S)-HpETE:

15S-Hydroperoxy-5Z,8Z,11Z,13E-eicosatetraenoic acid

17(18)-EpETE:

(±)17(18)-Epoxy-5Z,8Z,11Z,14Z-eicosatetraenoic acid

17,18-DiHETE:

17,18-Dihydroxy-5Z,8Z,11Z,14Z-eicosatetraenoic acid

20-HETE:

20-Hydroxy-5Z,8Z,11Z,14Z-eicosatetraenoic acid

20-HETE-d6 :

20-Hydroxy-5Z,8Z,11Z,14Z-eicosatetraenoic-16,16,17,17,18,18-d6 acid

References

  1. Vrablik TL, Watts JL (2013) Polyunsaturated fatty acid derived signaling in reproduction and development: insights from Caenorhabditis elegans and Drosophila melanogaster. Mol Reprod Dev 80:244–259. doi:10.1002/mrd.22167

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Evans JH, Spencer DM, Zweifach A, Leslie CC (2001) Intracellular calcium signals regulating cytosolic phospholipase A2 translocation to internal membranes. J Biol Chem 276:30150–30160. doi:10.1074/jbc.M100943200

    Article  CAS  PubMed  Google Scholar 

  3. Panigrahy D, Kaipainen A, Greene ER, Huang S (2010) Cytochrome P450-derived eicosanoids: the neglected pathway in cancer. Cancer Metastasis Rev 29:723–735. doi:10.1007/s10555-010-9264-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Kremmyda L, Tvrzicka E, Stankova B, Zak A (2011) Fatty acids as biocompounds: their role in human metabolism, health and disease-a review. Part 2: fatty acid physiological roles and applications in human health and disease. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 155:195–218. doi:10.5507/bp.2011.052

    Article  CAS  PubMed  Google Scholar 

  5. Qi Y (2014) Comparative modeling and functional characterization of two enzymes of the cyclooxygenase pathway in Drosophila melanogaster. Dissertation, City University of New York, New York 147

  6. Stanley-Samuelson DW (1994) The biological significance of prostaglandins and related eicosanoids in invertebrates. Am Zool 34:589–598. doi:10.1016/0965-1748(95)00092-5

    Article  CAS  Google Scholar 

  7. Stanley Samuelson DW, Jurenka RA, Cripps C, Blomquist GJ, de Renobales M (1988) Fatty acids in insects: composition, metabolism, and biological significance. Arch Insect Biochem Physiol 9:1–33

    Article  CAS  Google Scholar 

  8. Mckechnie SW, Geer BW (1993) Long-chain dietary fatty acids affect the capacity of Drosophila melanogaster to tolerate ethanol. J Nutr 123:106–116

    CAS  PubMed  Google Scholar 

  9. Ruden DM, De Luca M, Garfinkel MD, Bynum KL, Lu X (2005) Drosophila nutrigenomics can provide cluds to human gene-nutrient interactions. Annu Rev Nutr 25:499–522. doi:10.1146/annurev.nutr.25.050304.092708

    Article  CAS  PubMed  Google Scholar 

  10. Zhonghua L, Xun H (2013) Lipid metabolism in Drosophila: development and disease. Acta Biochim Biophys Sin 45:44–50. doi:10.1093/abbs/gms105

    Article  Google Scholar 

  11. Baker KD, Thummel CS (2007) Diabetic larvae and obese flies-emerging studies of metabolism in Drosophila. Cell Metab 6:257–266. doi:10.1016/j.cmet.09.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Kühnlein RP (2012) Lipid droplet-based storage fat metabolism in Drosophila thematic review series: lipid droplet synthesis and metabolism: from yeast to man. J Lipid Res 53:1430–1436. doi:10.1194/jlr.R024299

    Article  PubMed  PubMed Central  Google Scholar 

  13. Shen LR, Lai CQ, Feng X, Parnell LD, Wan JB, Wang JD, Li D, Ordovas JM, Kang JX (2010) Drosophila lacks C20 and C22 PUFA. J Lipid Res 51:2985–2992. doi:10.1194/jlr.M008524

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Yoshioka T, Inoue H, Kasama T, Seyama Y, Nakashima S, Nozawa Y, Hotta Y (1985) Evidence that arachidonic acid is deficient in phosphatidylinositol of Drosophila heads. J Biochem 98:657–662

    CAS  PubMed  Google Scholar 

  15. Jones HE, Harwood JL, Bowen ID, Griffiths G (1992) Lipid composition of subcellular membranes from larvae and prepupae of Drosophila melanogaster. Lipids 27:984–987

    Article  CAS  PubMed  Google Scholar 

  16. Funk CD (2001) Prostaglandins and leukotrienes: advances in eicosanoid biology. Science 294:1871–1875. doi:10.1126/science.294.5548.1871

    Article  CAS  PubMed  Google Scholar 

  17. Rapport EW, Stanley Samuelson D, Dadd RH (1983) Ten generations of Drosophila melanogaster reared axenically on a fatty acid-free holidic diet. Arch Insect Biochem Physiol 1:243–250

    Article  Google Scholar 

  18. Dzitoyeva S, Dimitrijevic N, Manev H (2003) Identification of a novel Drosophila gene, beltless, using injectable embryonic and adult RNA interference (RNAi). BMC Genom 4:33. doi:10.1186/1471-2164-4-33

    Article  Google Scholar 

  19. Elphick MR, Egertová M (2005) The phylogenetic distribution and evolutionary origins of endocannabinoid signaling. Handb Exp Pharmacol 168:283–297. doi:10.1007/3-540-26573-2-9

    Article  CAS  PubMed  Google Scholar 

  20. Mcpartland JM, Matias I, Di Marzo V (2006) Glass M. Evolutionary origins of the endocannabinoid system. Gene 370:64–74. doi:10.1016/j.gene.2005.11.004

    Article  CAS  PubMed  Google Scholar 

  21. Stanley D (2006) Prostaglandins and other eicosanoids in insects: biological significance. Annu Rev Entomol 51:25–44. doi:10.1146/annurev.ento.51.110104.151021

    Article  CAS  PubMed  Google Scholar 

  22. Gualde N, Rigaud M (1986) Cyclooxygenase and lipoxygenase-like activity in Drosophila melanogaster. Prostaglandins 32:729–740

    PubMed  Google Scholar 

  23. Hyrsl P, Dobes P, Wang Z, Hauling T, Wilhelmsson C, Theopold U (2011) Clotting factors and eicosanoids protect against nematode infections. J Innate Immun 3:65–70. doi:10.1159/000320634

    Article  PubMed  Google Scholar 

  24. Tootle TL, Spradling AC (2008) Drosophila Pxt: a cyclooxygenase-like facilitator of follicle maturation. Development 135:839–847. doi:10.1242/dev.017590

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Troen AM, French EE, Roberts JF, Selhub J Ordovas JM, Parnell LD, Lai CQ (2007) Lifespan modifi cation by glucose and methionine in Drosophila melanogaster fed a chemically defi ned diet. Age 29:29–39. doi:10.1007/s11357-006-9018-4 (Epub 2006 Nov 25)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Kang JX, Wang J (2005) A simplified method for analysis of polyunsaturated fatty acids. BMC Biochem 6:5. doi:10.1016/S0378-1119(00)00246-8

    Article  PubMed  PubMed Central  Google Scholar 

  27. Gomolka B, Siegert E, Blossey K, Schunck W, Rothe M, Weylandt KH (2011) Analysis of omega-3 and omega-6 fatty acid-derived lipid metabolite formation in human and mouse blood samples. Prostaglandins Other Lipid Mediat 94:81–87. doi:10.1016/j.prostaglandins.2010.12.006

    Article  CAS  PubMed  Google Scholar 

  28. Brose SA, Thuen BT, Golovko MY (2011) LC/MS/MS method for analysis of E 2 series prostaglandins and isoprostanes. J Lipid Res 52:850–859. doi:10.1194/jlr.D013441

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Jeffries KA, Dempsey DR, Behari AL, Anderson RL, Merkler DJ (2014) Drosophila melanogaster as a model system to study long-chain fatty acid amide metabolism. FEBS Lett 588:1596–1602. doi:10.1016/j.febslet

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Crawford MA, Casperd NM, Sinclair AJ (1976) The long chain metabolites of linoleic and linolenic acids in liver and brain in herbivores and carnivores. Comp. Biochem Physiol B 54B:395–401. doi:10.1016/0305-0491(76)90264-9

    Google Scholar 

  31. Yajima M, Takada M, Takahashi N, Kikuchi H, Natori S, Oshima Y, Kurata S (2003) A newly established in vitro culture using transgenic Drosophila reveals functional coupling between the phospholipase A2-generated fatty acid cascade and lipopolysaccharide-dependent activation of the immune deficiency (imd) pathway in insect immunity. Biochem J 371:205–210. doi:10.1042/BJ20021603

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Carton Y, Frey F, Stanley DW, Vass E, Nappi AJ (2002) Dexamethasone inhibition of the cellular Immune response of Drosophila melanogaster against a parasitoid. J Parasitol 88:405–407

    Article  CAS  PubMed  Google Scholar 

  33. Varvas K, Kurg R, Hansen K, Järving R, Järving I, Valmsen K, Lõhelaid H, Samel N (2009) Direct evidence of the cyclooxygenase pathway of prostaglandin synthesis in arthropods: genetic and biochemical characterization of two crustacean cyclooxygenases. Insect Biochem Mol Biol 39:851–860. doi:10.1016/j.ibmb.10.002

    Article  CAS  PubMed  Google Scholar 

  34. OvergARArd J, Sørensen JG, Petersen SO, Loeschcke V, Holmstrup M (2005) Changes in membrane lipid composition following rapid cold hardening in Drosophila melanogaster. J Insect Physiol 51:1173–1182. doi:10.1016/j.jinsphys.06.007

    Article  Google Scholar 

  35. Chang KH, Park JH, Lee YH, Kim JH, Chun HO, Kim JH, Chung IS (2002) Dimethylsulfoxide and sodium butyrate enhance the production of recombinant cyclooxygenase 2 in stably transformed Drosophila melanogaster S2 cells. Biotechnol Lett 24:1353–1359

    Article  CAS  Google Scholar 

  36. Toba G, Aigaki T (2000) Disruption of the Microsomal glutathione S-transferase-like gene reduces life span of Drosophila melanogaster. Gene 253:179–187. doi:10.1016/S0378-1119(00)00246-8

    Article  CAS  PubMed  Google Scholar 

  37. Mushegian AR, Garey JR, Martin J, Liu LX (1998) Large-scale taxonomic profiling of eukaryotic model organisms: a comparison of orthologous proteins encoded by the human, fly, nematode, and yeast genomes. Genome Res 8:590–598

    CAS  PubMed  Google Scholar 

  38. Caffrey RC, Rohwer A, Oellien F, Marhöfer RJ, Braschi S, Oliveira G, McKerrow JH, Selzer PM (2009) A Comparative chemogenomics strategy to predict potential drug Targets in the metazoan pathogen, schistosoma mansoni. PLoS One 4:e4413. doi:10.1371/journal.pone.0004413

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

The present study was supported by grants from the National Natural Science Foundation of China (No. 31271848), the Important Scientific and Technical Innovation Project of Hangzhou (No. 20131812A25) and the Foundation of Fuli Institute of Food Science, Zhejiang University (No. KY201404). The authors wish to thank Prof Andrew J Sinclair, School of Medicine Deakin University, Australia, and Dr. Chao-Qiang Lai, JM-USDA Human Nutrition Research Center on Aging at Tufts University, United States for revising the manuscript, Prof Guonian Zhu and Dr. Mei Yang, College of Agriculture and Biotechnology, Zhejiang University, for providing equipment of UPLC–MS/MS and technical assistance.

Author information

Authors and Affiliations

  1. Zhejiang Key Laboratory for Agro-Food Processing, Department of Food Science and Nutrition, Fuli Institute of Food Science, Zhejiang University, Hangzhou, 310058, China

    Liangliang Tan, Xiaoxuan Xin, Liang Zhai & Lirong Shen

Authors
  1. Liangliang Tan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xiaoxuan Xin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Liang Zhai
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lirong Shen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lirong Shen.

Ethics declarations

Conflict of interest

All authors have no conflict of interest in connection with this manuscript.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tan, L., Xin, X., Zhai, L. et al. Drosophila Fed ARA and EPA Yields Eicosanoids, 15S-Hydroxy-5Z,8Z, 11Z, 13E-Eicosatetraenoic Acid, and 15S-Hydroxy-5Z,8Z,11Z,13E,17Z-Eicosapentaenoic Acid. Lipids 51, 435–449 (2016). https://doi.org/10.1007/s11745-016-4131-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11745-016-4131-3

Keywords

Search

Navigation