Summary of Study ST002569
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 PR001656. The data can be accessed directly via it's Project DOI: 10.21228/M8ND9B This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.
| Study ID | ST002569 |
| Study Title | Lipidomic analysis in very-long chain acyl-CoA dehydrogenase null mice |
| Study Summary | Compared to their littermate counterparts, HFD/fasted VLCAD-/- mouse hearts displayed higher VLC-acylcarnitines accumulation, higher levels of arachidonic acid (AA) and lower docosahexaenoic acid (DHA) contents in glycerophospholipids (GPLs). |
| Institute | Montreal Heart Institute |
| Last Name | Forest |
| First Name | Anik |
| Address | 5000 Bélanger Street |
| metabolomique.icm@mhi-rc.org | |
| Phone | 5143763330 ext 2133 |
| Submit Date | 2023-04-11 |
| Analysis Type Detail | LC-MS |
| Release Date | 2023-09-06 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Project:
| Project ID: | PR001656 |
| Project DOI: | doi: 10.21228/M8ND9B |
| Project Title: | Remodeling of lipid landscape in high fat fed very-long chain acyl-CoA dehydrogenase null mice favors pro-arrhythmic polyunsaturated fatty acids and their downstream metabolites |
| Project Summary: | Very-long chain acyl-CoA dehydrogenase (VLCAD) catalyses mitochondrial fatty acid β-oxidation (FAO). Inherited VLCAD deficiency (VLCADD) predisposes to neonatal arrhythmias whose pathophysiology is still not understood. We hypothesized that VLCADD results in global disruption of cardiac complex lipid homeostasis, which may set conditions predisposing to arrhythmia. To test this, we assessed the cardiac lipidome and related molecular markers in seven-month-old VLCAD-/- mice, which mimic to some extent the human cardiac phenotype. Mice were sacrificed in the fed or fasted state after receiving for two weeks a chow or a high-fat diet (HFD), the latter condition being known to worsen symptoms in human VLCADD. Compared to their littermate counterparts, HFD/fasted VLCAD-/- mouse hearts displayed the following lipid alterations: (1) Lower LC, but higher VLC-acylcarnitines accumulation, (2) higher levels of arachidonic acid (AA) and lower docosahexaenoic acid (DHA) contents in glycerophospholipids (GPLs), as well as (3) corresponding changes in pro-arrhythmogenic AA-derived isoprostanes and thromboxane B2 (higher), and anti-arrythmogenic DHA-derived neuroprostanes (lower). These changes were associated with remodeling in the expression of gene or protein markers of (1) PL remodeling: higher calcium-dependent phospholipase A2 and lysophosphatidylcholine-acyltransferase 2, (2) calcium handling perturbations: higher SERCA2a and phospholamban, but lower RyR2, and (3) endoplasmic reticulum stress: higher CHOP and GRP78. Altogether, these results highlight global lipid dyshomeostasis beyond FAO in VLCAD-/- mouse hearts, which may set conditions predisposing the hearts to calcium mishandling and endoplasmic reticulum stress and thereby may contribute to the pathogenesis of arrhythmias in VLCADD in mice as well as in humans. |
| Institute: | Montreal Heart Institute |
| Last Name: | Forest |
| First Name: | Anik |
| Address: | 5000 Bélanger Street |
| Email: | metabolomique.icm@mhi-rc.org |
| Phone: | 5143763330 ext 2133 |
