Journal
PROSTAGLANDINS & OTHER LIPID MEDIATORS
Volume 148, Issue -, Pages -Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.prostaglandins.2020.106410
Keywords
FFA epoxide; Diol; Metabolomic analysis; Modeling
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Funding
- ADA Basic Science [1-16-IBS-332]
- West Coast Metabolomics Center at UC Davis [R01MH106781]
- NIEHS RIVER [R35 ES030443, NIEHS/R01 ES002710]
- NIEHS/Superfund Research Program [P42 ES004699]
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Soluble epoxide hydrolase (sEH) converts several FFA epoxides to corresponding diols. As many as 15 FFA epoxide-diol ratios are measured to infer sEH activity from their ratios. Using previous data, we assessed if individual epoxide-diol ratios all behave similarly to reflect changes in sEH activity, and whether analyzing these ratios together increases the power to detect changes in in-vivo sEH activity. We demonstrated that epoxide-diol ratios correlated strongly with each other (P < 0.05), suggesting these ratios all reflect changes in sEH activity. Furthermore, we developed a modeling approach to analyze all epoxide-diol ratios simultaneously to infer global sEH activity, named SAMI (Simultaneous Analysis of Multiple Indices). SAMI improved power in detecting changes in sEH activity in animals and humans when compared to individual ratio estimates. Thus, we introduce a new powerful method to infer sEH activity by combining metabolomic determination and simultaneous analysis of all measurable epoxide-diol pairs.
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