Summary of project PR001890

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001890. The data can be accessed directly via it's Project DOI: 10.21228/M8DQ64 This work is supported by NIH grant, U2C- DK119886.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

Project ID: PR001890
Project DOI:doi: 10.21228/M8DQ64
Project Title:Untargeted lipidomics of WT and Cyp2c44(-/-) mice liver.
Project Type:Untargeted Lipidomics
Project Summary:Cytochrome P450 epoxygenase Cyp2c44 and their metabolite epoxyeicosatrienoic acids or EETs promotes insulin sensitivity. Mice lacking Cyp2c44 exhibits hepatic insulin resistance. Insulin resistance is also intricately related to increased hepatic lipid accumulation and hyperlipidemia. Interestingly, Cyp2c44(-/-) mice in standard chow diet had significantly increased hepatic and plasma lipid levels compared to wild-type mice. To identify the nature of these lipids, with a focus on fatty acids, we performed lipidomic analysis of liver homogenates from SD-fed WT and Cyp2c44(-/-) mice. We identified 2425 lipids (1152 in negative mode and 1273 in positive mode) that passed both quality control filters set as 25% for QC RSD and 10% for QC/blank ratio. Principal component analysis revealed two distinct lipid clusters in livers of WT and Cyp2c44(-/-) mice. Heatmap analysis revealed a hierarchical clustering of significant differences occurring in lipid species between WT and Cyp2c44(-/-) livers. Volcano plot analysis of the 1152 lipids identified in the negative mode (which contain fatty acids) revealed 160 lipid species upregulated, 61 downregulated, and 931 not significantly changed in Cyp2c44(-/-) livers compared to WT livers. Analysis of fatty acids classes in negative mode identified a total of 146 fatty acids, with 49 upregulated, 3 downregulated and 94 unchanged in Cyp2c44(-/-) compared to WT livers. Among the fatty acids that are significantly upregulated in the livers of Cyp2c44(-/-), we detected the saturated fatty acids palmitic acid; the monosaturated oleic acid; and the polyunsaturated arachidonic, linoleic, eicosapentaenoic and docosahexaenoic acids. Importantly, arachidonic acid is the major substrate of Cyp2c epoxygenases, although linoleic, eicosapentaenoic and docosahexaenoic acids are also efficient alternative substrates. We thus hypothesized that Cyp2c44 also governs hepatic lipid metabolism.
Institute:Vanderbilt University Medical Center
Department:Nephrology
Last Name:Ghoshal
First Name:Kakali
Address:B-3106 Medical Center North, 1161 21st Ave South, Nashville, TN 37232
Email:kakali.ghoshal@vumc.org
Phone:615-322-7729

Summary of all studies in project PR001890

Study IDStudy TitleSpeciesInstituteAnalysis
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ST003038 Untargeted lipidomics of WT and Cyp2c44(-/-) mice liver. Mus musculus Vanderbilt University Medical Center MS 2024-01-25 1 20 Uploaded data (900.6M)*
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