Juniperonic Acid Biosynthesis is Essential in Caenorhabditis elegans Lacking Δ6 Desaturase (fat-3) and Generates New ω-3 Endocannabinoids
Abstract
:1. Introduction
2. Materials and Methods
2.1. Strains and Growth Conditions
2.2. Dietary Lipid Supplementation
2.3. Brood Size Assay and Development Monitoring
2.4. Lifespan Assays
2.5. RNA Interference by Feeding
2.6. Synthesis of the Endocannabinoid-Like Molecules Juniperoyl Ethanolamide (JEA) and ω-3 Arachidonoyl Ethanolamine (ω-3 AEA)
2.7. Synthesis of the Endocannabinoid-Like Molecules 1/2-Juniperoylglycerol (1/2-JG) and ω-3 1/2-Arachidonoylglycerol (ω-3 1/2-AG)
2.8. Chromatographic Conditions Used for LC-MS/MS Targeted Metabolomics Analysis (Identification and Qquantification)
2.9. Quantitative Analysis of Targeted Analytes Using LC-MS/MS
2.10. Sample Preparation for LC-MS/MS Analysis
2.11. Biochemical Assays
2.12. NPR-32 Binding Assay
3. Results
3.1. Differential Expression of Eicosatetraenoic Acids in Wild Type and fat-3(wa22) Mutant C. elegans
3.2. Recovery of fat-3(wa22) Mutant Related Defects by Supplementation of JuA
3.3. Elucidation of JuA Biosynthesis in fat-3(wa22) Mutants
3.4. Detection of Different ω-3 Endocannabinoids in C. elegans WT and fat-3(wa22) Mutant Strain
3.5. Characterization of AA, ω-3 AA and JuA Aerived Endocannabinoids on Metabolic Enzymes and NPR-32 and NPR-19 Binding
4. Discussion
Author Contributions
Supplementary Materials
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
1/2-AG | 1/2-arachidonoylglycerol |
1/2-JG | 1/2-juniperoylglycerol |
2-OG | 2-Mono-oleoyl-rac-glycerol |
AA | Arachidonic acid |
ACN | Acetonitrile |
AEA | N-arachidonoyl ethanolamine |
ALA | α-linoleic acid |
CCR2 | C-C motif chemokine receptor 2 |
CGC | Caenorhabditis Genetics Center |
CHCl3 | Chloroform |
CH3OH | Methanol |
DAGL | Diacylglycerol lipase |
DHGLA | Dihomo-gamma-linolenic acid |
ECs | Endocannabinoids |
ECS | Endocannabinoid system |
ELO 1/2 | Fatty acid eongases in C. elegans |
EPA | Eicosapentanenoic acid |
FAs | Fatty acids |
FAAH | Fatty acid amide hydrolase |
FADS2 | Fatty acid desaturase 2, gene of Δ6 desaturase |
FUDR | 5′-fluorodeoxyuridine |
GLA | Gamma linoleic acid |
GPCR | G protein coupled receptor |
HCl | Hydrogen chloride |
IPTG | Isopropyl-β-D-thiogalactopyranoside |
JEA | N-juniperoyl ethanolamine |
JuA | Juniperonic acid |
LA | Linoleic acid |
LC | Liquid chromatography |
MAGL | Monoacylglycerol lipase |
MgCl2 | Magnesium chloride |
NAE | N-acylethanolamine |
NAPE-PLD | N-acylphosphatidylethanolamine-hydrolyzing phospholipase D |
NGM | Nematode growth media |
NPR-19 | Cannabinoid G-protein coupled receptor in C. elegans |
NPR-32 | Cannabinoid G-protein coupled receptor in C. elegans |
PUFAs | Polyunsaturated fatty acids |
ScA | Sciadonic acid |
ω -3 AEA | Omega-3 N-arachidonoyl ethanolamine |
ω -3 1/2-AG | Omega-3 1/2-arachidonoyl glycerol |
ω-3 AA | Omega-3 arachidonic acid |
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Fatty Acids | WT | fat-3 (wa22) |
---|---|---|
Arachidonic acid (AA) | + | - |
ω-3 arachidonic acid (ω-3 AA) | + | - |
Juniperonic acid (JuA) | - | + |
α-linoleic acid (ALA) | - | + |
γ-linoleic acid (GLA) | + | - |
Sciadonic acid (ScA) | - | - |
dihomo-γ-linoleic acid (DHGLA) | + | - |
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Guha, S.; Calarco, S.; Gachet, M.S.; Gertsch, J. Juniperonic Acid Biosynthesis is Essential in Caenorhabditis elegans Lacking Δ6 Desaturase (fat-3) and Generates New ω-3 Endocannabinoids. Cells 2020, 9, 2127. https://doi.org/10.3390/cells9092127
Guha S, Calarco S, Gachet MS, Gertsch J. Juniperonic Acid Biosynthesis is Essential in Caenorhabditis elegans Lacking Δ6 Desaturase (fat-3) and Generates New ω-3 Endocannabinoids. Cells. 2020; 9(9):2127. https://doi.org/10.3390/cells9092127
Chicago/Turabian StyleGuha, Sujay, Serafina Calarco, M. Salomé Gachet, and Jürg Gertsch. 2020. "Juniperonic Acid Biosynthesis is Essential in Caenorhabditis elegans Lacking Δ6 Desaturase (fat-3) and Generates New ω-3 Endocannabinoids" Cells 9, no. 9: 2127. https://doi.org/10.3390/cells9092127