Epoxides Derived from Dietary Dihomo-Gamma-Linolenic Acid Induce Germ Cell Death in C. elegans.
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.
School of Molecular Biosciences and Center for Reproductive Biology, Washington State University, Pullman, WA 99614-6340, USA.
Marshall
M
Deline
Humboldt-Universität zu Berlin, Department of Biology, Ecology, Philippstr. 13, House 18, 10115 Berlin, Germany.
Julia
J
Keller
Lipidomix GmbH, Robert-Rössle-Str. 10, 13125 Berlin, Germany.
Michael
M
Rothe
Max Delbrück Center for Molecular Medicine, Robert-Rössle-Str. 10, 13125 Berlin, Germany.
Wolf-Hagen
WH
Schunck
Humboldt-Universität zu Berlin, Department of Biology, Ecology, Philippstr. 13, House 18, 10115 Berlin, Germany.
Ralph
R
Menzel
School of Molecular Biosciences and Center for Reproductive Biology, Washington State University, Pullman, WA 99614-6340, USA.
Jennifer L
JL
Watts
D015126:8,11,14-Eicosatrienoic Acid / Q000008:administration & dosage* / Q000737:chemistry; D000818:Animals; D017173:Caenorhabditis elegans / Q000187:drug effects; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects*; D002790:Cholesterol 7-alpha-Hydroxylase / Q000378:metabolism*; D004032:Diet; D004041:Dietary Fats / Q000378:metabolism; D004852:Epoxy Compounds / Q000008:administration & dosage* / Q000737:chemistry; D005854:Germ Cells / Q000187:drug effects*
D029742:Caenorhabditis elegans Proteins; D004041:Dietary Fats; D004852:Epoxy Compounds; C000610640:CYP-33E2 protein, C elegans; D002790:Cholesterol 7-alpha-Hydroxylase; D015126:8,11,14-Eicosatrienoic Acid