Summary of Study ST003472

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 PR002131. The data can be accessed directly via it's Project DOI: 10.21228/M85G08 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	ST003472
Study Title	An optimized plasmalogen modulating dietary supplement provides greater protection in a male than female mouse model of dilated cardiomyopathy
Study Summary	We previously reported that plasmalogens, a class of phospholipids, were decreased in a setting of dilated cardiomyopathy (DCM). Plasmalogen levels can be modulated via a dietary supplement called alkylglycerols (AG) which has demonstrated benefits in some disease settings. However, its therapeutic potential in DCM remained unknown. To determine whether an optimized AG supplement could restore plasmalogen levels and attenuate cardiac dysfunction/pathology, we placed a cardiac-specific transgenic DCM mouse model of both sexes on chow +/- 1.5% AG supplementation at ~10 weeks of age for 16 weeks. Cardiac function was assessed by echocardiography, tissues were collected for histological and molecular analyses including lipidomics and proteomics via liquid chromatography-mass spectrometry. AG supplementation increased total plasmalogens in DCM hearts and attenuated lung congestion of both sexes, but only prevented cardiac dysfunction in males. This was associated with attenuated cardiac and renal enlargement, a more favorable pro-cardiac gene expression profile, and a trend for lower cardiac fibrosis. By lipidomics, specific d18:1 ceramide species associated with cardiac pathology were lower in the DCM hearts from mice on the AG diet, and tetra-linoleoyl cardiolipin, a lipid crucial for mitochondria function was restored with AG supplementation. Proteomic analysis of hearts from male DCM mice receiving AG supplementation revealed enrichment in mitochondrial protein network, as well as upregulation of extracellular matrix binding proteins including agrin, a protein associated with cardiac regeneration. In summary, AG supplementation restored plasmalogens in DCM hearts, but showed greater therapeutic potential in males than females.
Institute	Baker Heart and Diabetes Institute
Department	Discovery and Preclinical Science
Laboratory	Cardiac Hypertrophy
Last Name	Belkin
First Name	Teleah
Address	75 Commercial Road, Melbourne, Victoria, 3004, Australia
Email	teleah.belkin@baker.edu.au
Phone	+65385321266
Submit Date	2024-08-26
Num Groups	4
Total Subjects	71
Num Males	34
Num Females	37
Raw Data Available	Yes
Raw Data File Type(s)	d, mzML
Analysis Type Detail	LC-MS
Release Date	2024-12-06
Release Version	1

Select appropriate tab below to view additional metadata details:

Project:

Project ID:	PR002131
Project DOI:	doi: 10.21228/M85G08
Project Title:	Lipidomic profiling of heart and plasma of male and female DCM mice
Project Summary:	Ventricles and plasma of male and female Ntg and dilated cardiomyopathy (DCM) mice subjected to chow or alkylglycerol supplementation (1.5% of total chow) from 10 weeks of age to 26 weeks of age (supplementation for 16 weeks). Males: Ntg Chow n=7, Ntg Diet n=7, DCM Chow n=8, DCM Diet n=12. Females: Ntg Chow n=11, Ntg Diet n=11, DCM Chow n=8, DCM Diet n=7 were subjected to lipidomic profiling.
Institute:	Baker Heart and Diabetes Institute
Department:	Discovery and Preclinical Science
Laboratory:	Cardiac Hypertrophy
Last Name:	Belkin
First Name:	Teleah
Address:	75 Commercial Road, Melbourne, Victoria, 3004, Australia
Email:	teleah.belkin@baker.edu.au
Phone:	+65385321266
Publications:	https://doi.org/10.1016/j.jmccpl.2024.100273

Subject:

Subject ID:	SU003600
Subject Type:	Mammal
Subject Species:	Mus musculus
Taxonomy ID:	10090
Genotype Strain:	C57BL6
Age Or Age Range:	26 weeks
Gender:	Male and female
Animal Light Cycle:	12-hour light-dark cycle environment (6am-6pm)
Animal Feed:	Specialty Feeds Irradiated Rat and Mouse Standard Chow Diet or 1.5% alkylglycerols per 100g of chow
Species Group:	Mammals

Factors:

Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)

mb_sample_id	local_sample_id	Sex	Genotype	Diet	Sample source
SA383272	38738_Plasma	Female	DCM	Chow	Plasma
SA383273	39372_Plasma	Female	DCM	Chow	Plasma
SA383274	39374_Plasma	Female	DCM	Chow	Plasma
SA383275	39382_Plasma	Female	DCM	Chow	Plasma
SA383276	38708_Plasma	Female	DCM	Chow	Plasma
SA383277	39371_Plasma	Female	DCM	Chow	Plasma
SA383278	39013_Plasma	Female	DCM	Chow	Plasma
SA383279	38736_Plasma	Female	DCM	Chow	Plasma
SA383280	38736_Vent	Female	DCM	Chow	Ventricle
SA383281	39371_Vent	Female	DCM	Chow	Ventricle
SA383282	39013_Vent	Female	DCM	Chow	Ventricle
SA383283	38708_Vent	Female	DCM	Chow	Ventricle
SA383284	39382_Vent	Female	DCM	Chow	Ventricle
SA383285	39374_Vent	Female	DCM	Chow	Ventricle
SA383286	39372_Vent	Female	DCM	Chow	Ventricle
SA383287	38738_Vent	Female	DCM	Chow	Ventricle
SA383288	39376_Plasma	Female	DCM	Diet	Plasma
SA383289	38730_Plasma	Female	DCM	Diet	Plasma
SA383290	39375_Plasma	Female	DCM	Diet	Plasma
SA383291	39380_Plasma	Female	DCM	Diet	Plasma
SA383292	39384_Plasma	Female	DCM	Diet	Plasma
SA383293	38719_Plasma	Female	DCM	Diet	Plasma
SA383294	39010_Plasma	Female	DCM	Diet	Plasma
SA383295	39375_Vent	Female	DCM	Diet	Ventricle
SA383296	39376_Vent	Female	DCM	Diet	Ventricle
SA383297	39384_Vent	Female	DCM	Diet	Ventricle
SA383298	39010_Vent	Female	DCM	Diet	Ventricle
SA383299	39380_Vent	Female	DCM	Diet	Ventricle
SA383300	38719_Vent	Female	DCM	Diet	Ventricle
SA383301	38730_Vent	Female	DCM	Diet	Ventricle
SA383302	38716_Plasma	Female	Ntg	Chow	Plasma
SA383303	39383_Plasma	Female	Ntg	Chow	Plasma
SA383304	39381_Plasma	Female	Ntg	Chow	Plasma
SA383305	38707_Plasma	Female	Ntg	Chow	Plasma
SA383306	38715_Plasma	Female	Ntg	Chow	Plasma
SA383307	39370_Plasma	Female	Ntg	Chow	Plasma
SA383308	39022_Plasma	Female	Ntg	Chow	Plasma
SA383309	39014_Plasma	Female	Ntg	Chow	Plasma
SA383310	39023_Plasma	Female	Ntg	Chow	Plasma
SA383311	38737_Plasma	Female	Ntg	Chow	Plasma
SA383312	39373_Plasma	Female	Ntg	Chow	Plasma
SA383313	38716_Vent	Female	Ntg	Chow	Ventricle
SA383314	38715_Vent	Female	Ntg	Chow	Ventricle
SA383315	39370_Vent	Female	Ntg	Chow	Ventricle
SA383316	39383_Vent	Female	Ntg	Chow	Ventricle
SA383317	39373_Vent	Female	Ntg	Chow	Ventricle
SA383318	39381_Vent	Female	Ntg	Chow	Ventricle
SA383319	39023_Vent	Female	Ntg	Chow	Ventricle
SA383320	39022_Vent	Female	Ntg	Chow	Ventricle
SA383321	38707_Vent	Female	Ntg	Chow	Ventricle
SA383322	39014_Vent	Female	Ntg	Chow	Ventricle
SA383323	38737_Vent	Female	Ntg	Chow	Ventricle
SA383324	39385_Plasma	Female	Ntg	Diet	Plasma
SA383325	39377_Plasma	Female	Ntg	Diet	Plasma
SA383326	38725_Plasma	Female	Ntg	Diet	Plasma
SA383327	39011_Plasma	Female	Ntg	Diet	Plasma
SA383328	38728_Plasma	Female	Ntg	Diet	Plasma
SA383329	39379_Plasma	Female	Ntg	Diet	Plasma
SA383330	39012_Plasma	Female	Ntg	Diet	Plasma
SA383331	39378_Plasma	Female	Ntg	Diet	Plasma
SA383332	38729_Plasma	Female	Ntg	Diet	Plasma
SA383333	38706_Plasma	Female	Ntg	Diet	Plasma
SA383334	39025_Plasma	Female	Ntg	Diet	Plasma
SA383335	39025_Vent	Female	Ntg	Diet	Ventricle
SA383336	39378_Vent	Female	Ntg	Diet	Ventricle
SA383337	38725_Vent	Female	Ntg	Diet	Ventricle
SA383338	39379_Vent	Female	Ntg	Diet	Ventricle
SA383339	39012_Vent	Female	Ntg	Diet	Ventricle
SA383340	39385_Vent	Female	Ntg	Diet	Ventricle
SA383341	39011_Vent	Female	Ntg	Diet	Ventricle
SA383342	39377_Vent	Female	Ntg	Diet	Ventricle
SA383343	38706_Vent	Female	Ntg	Diet	Ventricle
SA383344	38729_Vent	Female	Ntg	Diet	Ventricle
SA383345	38728_Vent	Female	Ntg	Diet	Ventricle
SA383271	-	-	-	-	-
SA383346	38710_Plasma	Male	DCM	Chow	Plasma
SA383347	38735_Plasma	Male	DCM	Chow	Plasma
SA383348	38731_Plasma	Male	DCM	Chow	Plasma
SA383349	38733_Plasma	Male	DCM	Chow	Plasma
SA383350	38734_Plasma	Male	DCM	Chow	Plasma
SA383351	39015_Plasma	Male	DCM	Chow	Plasma
SA383352	32210_Plasma	Male	DCM	Chow	Plasma
SA383353	38717_Plasma	Male	DCM	Chow	Plasma
SA383354	38717_Vent	Male	DCM	Chow	Ventricle
SA383355	32210_Vent	Male	DCM	Chow	Ventricle
SA383356	39015_Vent	Male	DCM	Chow	Ventricle
SA383357	38710_Vent	Male	DCM	Chow	Ventricle
SA383358	38734_Vent	Male	DCM	Chow	Ventricle
SA383359	38735_Vent	Male	DCM	Chow	Ventricle
SA383360	38731_Vent	Male	DCM	Chow	Ventricle
SA383361	38733_Vent	Male	DCM	Chow	Ventricle
SA383362	38727_Plasma	Male	DCM	Diet	Plasma
SA383363	39018_Plasma	Male	DCM	Diet	Plasma
SA383364	38743_Plasma	Male	DCM	Diet	Plasma
SA383365	38740_Plasma	Male	DCM	Diet	Plasma
SA383366	38739_Plasma	Male	DCM	Diet	Plasma
SA383367	38742_Plasma	Male	DCM	Diet	Plasma
SA383368	38726_Plasma	Male	DCM	Diet	Plasma
SA383369	38721_Plasma	Male	DCM	Diet	Plasma
SA383370	38720_Plasma	Male	DCM	Diet	Plasma

Showing page 1 of 2 Results: 1 2 Next Showing results 1 to 100 of 143

Collection:

Collection ID:	CO003593
Collection Summary:	Ventricles were dissected from mice. Tissues were snap frozen in liquid nitrogen and stored in -80 freezer until tissues were processed for lipid extractions Blood was collected via cardiac puncture and stored in EDTA tubes on ice. EDTA tubes were spun at 3000g for 15 mins at 4 degrees. Plasma was then collected from these tubes (supernatant) and then stored at -80 degrees.
Sample Type:	Heart
Storage Conditions:	-80℃
Collection Vials:	1.5mL Eppendorf tubes
Storage Vials:	1.5mL Eppendorf tubes

Treatment:

Treatment ID:	TR003609
Treatment Summary:	10-week-old Ntg and DCM mice were placed on chow or 1.5% AG supplementation for 16 weeks. Mice were fasted for 6 hours before dissections, and a lethal dose of anesthesia was delivered via intraperitoneal injection before tissue collection.
Treatment:	Dietary supplementation
Treatment Compound:	Alkylglycerols
Treatment Dose:	1.5% alkylglycerols per 100g of chow
Treatment Doseduration:	16 weeks
Treatment Vehicle:	Chow
Animal Anesthesia:	Sodium pentobarbitone
Animal Fasting:	6 hours

Sample Preparation:

Sampleprep ID:	SP003607
Sampleprep Summary:	Ventricles were homogenised in 1xPBS and then sonicated with a probe-sonicator for 15 seconds, 23 amplitude. BCA assays were then conducted to determine protein concentrations of these homogenates. Lipid extraction was conducted using 10ul of sample (ventricle, 5mg/ml) using the single-phase chloroform methanol method. 10ul of internal standards and 200ul of chloroform:methanol (1:2) were added to samples before the mixture was vortexed. Samples were then placed on a rotary shaker for 10 mins at a speed of 90 before being transferred to a bath sonicator. Samples were then sonicated for 30 mins at water temperature below 28 degrees. Samples were then removed and rested at room temperature for 20 mins. Samples were then centrifuged at 13000rpm for 10 minutes. 200ul of the supernatant was then transferred to 0.5ml polypropylene 96 well plates and spun dried using a speedvac vacuum concentrator. Lipids were reconstituted in 50ul water saturated butanol + 50ul of Ammonium Formate.
Sampleprep Protocol Filename:	Agilent_Protocol
Processing Storage Conditions:	-80℃
Extraction Method:	Chloroform:Methanol

Combined analysis:

Analysis ID	AN005707
Analysis type	MS
Chromatography type	Reversed phase
Chromatography system	Agilent 1290 Infinity II
Column	Agilent ZORBAX Eclipse Plus C18 (100 x 2.1mm,1.8um)
MS Type	ESI
MS instrument type	Triple quadrupole
MS instrument name	Agilent 6490 QQQ
Ion Mode	POSITIVE
Units	pmol per umol PC (ventricle) pmol per ml (plasma)

Chromatography:

Chromatography ID:	CH004329
Chromatography Summary:	The running solvent consisted of solvent A: 50% H2O / 30% acetonitrile / 20% isopropanol (v/v/v) containing 10mM ammonium formate and 5uM medronic acid, and solvent B: 1% H2O / 9% acetonitrile / 90% isopropanol (v/v/v) containing 10mM ammonium formate. We utilized a stepped linear gradient with a 16-minute cycle time per sample and a 1µL sample injection. To increase throughput, we used a dual column set up to equilibrate the second column while the first is running a sample. The sample analytical gradient was as follows: starting with a flow rate of 0.4mL/minute at 15% B and increasing to 50% B over 2.5 minutes, then to 57% over 0.1 minutes, to 70% over 6.4 minutes, to 93% over 0.1 minute, to 96% over 1.9 minutes and finally to 100% over 0.1 minute. The solvent was then held at 100% B for 0.9 minutes (total 12.0 minutes). Equilibration was started as follows: solvent was decreased from 100% B to 15% B over 0.2 minutes and held until a total of 16 minutes. The next sample is injected and the columns are switched.
Instrument Name:	Agilent 1290 Infinity II
Column Name:	Agilent ZORBAX Eclipse Plus C18 (100 x 2.1mm,1.8um)
Column Temperature:	45℃
Flow Gradient:	starting with a flow rate of 0.4mL/minute at 15% B and increasing to 50% B over 2.5 minutes, then to 57% over 0.1 minutes, to 70% over 6.4 minutes, to 93% over 0.1 minute, to 96% over 1.9 minutes and finally to 100% over 0.1 minute. The solvent was then held at 100% B for 0.9 minutes (total 12.0 minutes). Equilibration was started as follows: solvent was decreased from 100% B to 15% B over 0.2 minutes and held until a total of 16 minutes.
Flow Rate:	0.4 mL/min
Solvent A:	50% water/30% acetonitrile/20% isopropanol; 10mM ammonium formate; 5uM medronic acid
Solvent B:	1% water/9% acetonitrile/90% isopropanol; 10mM ammonium formate
Chromatography Type:	Reversed phase

MS:

MS ID:	MS005431
Analysis ID:	AN005707
Instrument Name:	Agilent 6490 QQQ
Instrument Type:	Triple quadrupole
MS Type:	ESI
MS Comments:	Analysis of ventricles and plasma extracts was performed on an Agilent 6490 QQQ mass spectrometer with an Agilent 1290 series HPLC system and a ZORBAX eclipse plus C18 column (2.1x100mm 1.8μm, Agilent) with the thermostat set at 60°C. Mass spectrometry analysis was performed in positive ion mode with dynamic scheduled multiple reaction monitoring (MRM). The following mass spectrometer conditions were used; gas temperature, 150°C, gas flow rate 17L/min, nebulizer 20psi, Sheath gas temperature 200°C, capillary voltage 3500V and sheath gas flow 10L/min. Isolation widths for Q1 and Q3 were set to “unit” resolution (0.7 amu).
Ion Mode:	POSITIVE
Analysis Protocol File:	Agilent_Protocol.pdf