Epoxides Derived from Dietary Dihomo-Gamma-Linolenic Acid Induce Germ Cell Death in C. elegans

Marshall Deline; Julia Keller; Michael Rothe; Wolf-Hagen Schunck; Ralph Menzel; Jennifer L Watts

doi:10.1038/srep15417

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Epoxides Derived from Dietary Dihomo-Gamma-Linolenic Acid Induce Germ Cell Death in C. elegans

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Epoxides Derived from Dietary Dihomo-Gamma-Linolenic Acid Induce Germ Cell Death in C. elegans

Marshall Deline, Julia Keller, Michael Rothe, Wolf-Hagen Schunck, Ralph Menzel and Jennifer L Watts

Scientific reports, Vol.5(1), pp.15417-15417

10/21/2015

DOI: https://doi.org/10.1038/srep15417

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https://hdl.handle.net/2376/107099

PMCID: PMC4614016

PMID: 26486965

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Abstract

Dietary Fats - metabolism

Animals

Caenorhabditis elegans - drug effects

Diet

Cholesterol 7-alpha-Hydroxylase - metabolism

Epoxy Compounds - administration & dosage

Epoxy Compounds - chemistry

Germ Cells - drug effects

8,11,14-Eicosatrienoic Acid - administration & dosage

8,11,14-Eicosatrienoic Acid - chemistry

Caenorhabditis elegans Proteins - metabolism

Cell Death - drug effects

Dietary fats are not created equally, slight differences in structure lead to crucial differences in function. Muticellular organisms use polyunsaturated fatty acid as substrates to produce potent signaling molecules crucial for many physiological processes, including reproduction. Here we explored the mechanism responsible for germ cell loss induced by dietary supplementation of dihomo-gamma-linolenic acid (DGLA, 20:3n-6) in the roundworm Caenorhabditis elegans. In this study we found that C. elegans CYP-33E2 activity produces a range of epoxy and hydroxy metabolites from dietary DGLA. Knockdown of cyp-33E2 suppressed the DGLA-induced sterility phenotype. Additionally, direct exposure of two specific DGLA-derived epoxy products, 8,9- and 14,15-epoxyeicosadienoic acids, produced germ cell abnormalities in the C. elegans gonad. We propose that sterility is mediated by the production of toxic DGLA-derived epoxides that trigger germ cell destruction. These studies are the first to establish a biological activity for a CYP-produced metabolite of DGLA.

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Title: Epoxides Derived from Dietary Dihomo-Gamma-Linolenic Acid Induce Germ Cell Death in C. elegans
Creators: Marshall Deline - School of Molecular Biosciences and Center for Reproductive Biology, Washington State University, Pullman, WA 99614-6340, USA
Julia Keller - Humboldt-Universität zu Berlin, Department of Biology, Ecology, Philippstr. 13, House 18, 10115 Berlin, Germany
Michael Rothe - Lipidomix GmbH, Robert-Rössle-Str. 10, 13125 Berlin, Germany
Wolf-Hagen Schunck - Max Delbrück Center for Molecular Medicine, Robert-Rössle-Str. 10, 13125 Berlin, Germany
Ralph Menzel - Humboldt-Universität zu Berlin, Department of Biology, Ecology, Philippstr. 13, House 18, 10115 Berlin, Germany
Jennifer L Watts - School of Molecular Biosciences and Center for Reproductive Biology, Washington State University, Pullman, WA 99614-6340, USA
Publication Details: Scientific reports, Vol.5(1), pp.15417-15417
Academic Unit: Molecular Biosciences, School of
Publisher: England
Grant note: R01 DK074114 / NIDDK NIH HHS R01 DK74114 / NIDDK NIH HHS P40 OD010440 / NIH HHS T32 GM083864 / NIGMS NIH HHS
Identifiers: 99900547090601842
Language: English
Resource Type: Journal article