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 |
Subject:
| Subject ID: | SU002670 |
| Subject Type: | Mammal |
| Subject Species: | Mus musculus |
| Taxonomy ID: | 10090 |
| Gender: | Male |
Factors:
Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)
| mb_sample_id | local_sample_id | Diet | Nutritional status | Genotype |
|---|---|---|---|---|
| SA258265 | 5973 | High Fat diet | Fasted | VLCAD -/- |
| SA258266 | 5974 | High Fat diet | Fasted | VLCAD -/- |
| SA258267 | 5972 | High Fat diet | Fasted | VLCAD -/- |
| SA258268 | 5971 | High Fat diet | Fasted | VLCAD -/- |
| SA258269 | 5970 | High Fat diet | Fasted | VLCAD -/- |
| SA258270 | 5975 | High Fat diet | Fasted | VLCAD -/- |
| SA258271 | 5976 | High Fat diet | Fasted | VLCAD -/- |
| SA258272 | 5980 | High Fat diet | Fasted | VLCAD -/- |
| SA258273 | 5978 | High Fat diet | Fasted | VLCAD -/- |
| SA258274 | 5979 | High Fat diet | Fasted | VLCAD -/- |
| SA258275 | 5977 | High Fat diet | Fasted | VLCAD -/- |
| SA258255 | 5964 | High Fat diet | Fasted | VLCAD +/+ |
| SA258256 | 5963 | High Fat diet | Fasted | VLCAD +/+ |
| SA258257 | 5962 | High Fat diet | Fasted | VLCAD +/+ |
| SA258258 | 5965 | High Fat diet | Fasted | VLCAD +/+ |
| SA258259 | 5967 | High Fat diet | Fasted | VLCAD +/+ |
| SA258260 | 5969 | High Fat diet | Fasted | VLCAD +/+ |
| SA258261 | 5968 | High Fat diet | Fasted | VLCAD +/+ |
| SA258262 | 5959 | High Fat diet | Fasted | VLCAD +/+ |
| SA258263 | 5966 | High Fat diet | Fasted | VLCAD +/+ |
| SA258264 | 5961 | High Fat diet | Fasted | VLCAD +/+ |
| SA258285 | 5701 | Standard diet | Fed | VLCAD -/- |
| SA258286 | 5699 | Standard diet | Fed | VLCAD -/- |
| SA258287 | 5702 | Standard diet | Fed | VLCAD -/- |
| SA258288 | 5700 | Standard diet | Fed | VLCAD -/- |
| SA258289 | 5704 | Standard diet | Fed | VLCAD -/- |
| SA258290 | 5696 | Standard diet | Fed | VLCAD -/- |
| SA258291 | 5698 | Standard diet | Fed | VLCAD -/- |
| SA258292 | 5697 | Standard diet | Fed | VLCAD -/- |
| SA258293 | 5703 | Standard diet | Fed | VLCAD -/- |
| SA258276 | 5689 | Standard diet | Fed | VLCAD +/+ |
| SA258277 | 5688 | Standard diet | Fed | VLCAD +/+ |
| SA258278 | 5690 | Standard diet | Fed | VLCAD +/+ |
| SA258279 | 5691 | Standard diet | Fed | VLCAD +/+ |
| SA258280 | 5695 | Standard diet | Fed | VLCAD +/+ |
| SA258281 | 5694 | Standard diet | Fed | VLCAD +/+ |
| SA258282 | 5687 | Standard diet | Fed | VLCAD +/+ |
| SA258283 | 5693 | Standard diet | Fed | VLCAD +/+ |
| SA258284 | 5692 | Standard diet | Fed | VLCAD +/+ |
| Showing results 1 to 39 of 39 |
Collection:
| Collection ID: | CO002663 |
| Collection Summary: | Mice were sacrificed under anesthesia using ketamine (100mg/ml) and xylazine (20mg/ml). Immediately after mouse sacrifice, hearts were rapidly excised, snap-frozen with liquid nitrogen, and then stored at -80°C. |
| Sample Type: | Heart |
| Storage Conditions: | -80℃ |
| Collection Tube Temp: | -80 |
Treatment:
| Treatment ID: | TR002682 |
| Treatment Summary: | VLCAD-/- males (129svJ X C57BL/6J genetic background) were crossed with C57Bl/6J females to generate heterozygous VLCAD+/- mice. Coupling of heterozygous mice then produced VLCAD-/- mice and control littermate counterparts (VLCAD+/+). All animals were genotyped as previously described. Mice were housed in a specific pathogen-free facility under a 12-h light/dark cycle at constant temperature and with access to water and food ad libitum. At 7-month of age, mice were fed for 2 weeks with either a chow diet (Harlan no. 2018; 3.1 kcal/g) or a high-fat diet (Harlan Teklab no. 3584; 5.4kcal/g) ad libitum. Mice were sacrificed in fed state for the CD group (CD/fed condition) or after fasting for 24 hours for the HFD group (HFD/fasted condition. Percent calories from carbohydrates, lipids and proteins were 58/18/24 for the CD and 26.6/58.4/15 for the HFD. |
Sample Preparation:
| Sampleprep ID: | SP002676 |
| Sampleprep Summary: | Total lipids were extracted from 40mg of pulverized hearts under liquid nitrogen using in methyl tert-butyl ether (MTBE) and ethyl acetate after spiking with the following internal standards lysophosphatidylcholine (LPC) 13:0, phosphatidylcholine (PC) 19:0/19:0, PC14:0/14:0, phosphatidylserine (PS) 12:0/12:0, phosphatidylglycerol (PG) 15:0/15:0 and phosphatidylethanolamine (PE) 17:0/17:0). Supernatants were evaporated using a Speed Vacuum concentrator overnight, dissolved in methanol/chloroform (2:1) and aliquots (50 µL) were stored at -80ºC until use. |
| Sampleprep Protocol Filename: | Sample preparation protocol of untargeted lipidomic analysis |
| Processing Storage Conditions: | -80℃ |
Combined analysis:
| Analysis ID | AN004233 |
|---|---|
| Analysis type | MS |
| Chromatography type | Reversed phase |
| Chromatography system | Agilent 1290 Infinity |
| Column | Agilent ZORBAX Eclipse Plus C18 (100 x 2.1mm,1.8um) |
| MS Type | ESI |
| MS instrument type | QTOF |
| MS instrument name | Agilent 6530 QTOF |
| Ion Mode | POSITIVE |
| Units | Counts |
Chromatography:
| Chromatography ID: | CH003141 |
| Methods Filename: | LC-MS and data processing protocol of untargeted lipidomic analysis |
| Instrument Name: | Agilent 1290 Infinity |
| Column Name: | Agilent ZORBAX Eclipse Plus C18 (100 x 2.1mm,1.8um) |
| Column Temperature: | 40 |
| Flow Gradient: | 0–2 min, 50% B; 2–11 min, 50–85% B; 11–33 min, 85–94% B; 33–35 min, 94–98% B, 35–38 min; 98–99.5% B; 38–82 min, 98–99.5% B; 82–83 min, 99.5–50% B, plus an equilibration of 8 min |
| Flow Rate: | 0.45 ml/min |
| Solvent A: | 100% water; 0.2% formic acid; 10 mM ammonium formate |
| Solvent B: | 55% ethanol,/35% acetonitrile/10% MTBE, 55:35:10; 0.2% formic acid; 10 mM ammonium formate |
| Chromatography Type: | Reversed phase |
MS:
| MS ID: | MS003980 |
| Analysis ID: | AN004233 |
| Instrument Name: | Agilent 6530 QTOF |
| Instrument Type: | QTOF |
| MS Type: | ESI |
| MS Comments: | MS data processing was achieved using the Mass Hunter Qualitative Analysis software package (version B.07) for peak picking and a bioinformatic script that we have developed and encoded in both Perl and R languages to enable optimal MS data alignment, filtering of presence, normalisation, batch effect correction, and missing data imputation. The resulting final dataset list reproducible high quality MS signals referred as features with their mass-over-charge (m/z), corrected signal intensity, and retention time (RT). Feature identity (ID) was as following: ionization mode:mass@RT. |
| Ion Mode: | POSITIVE |
