Summary of Study ST002228

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 PR001419. The data can be accessed directly via it's Project DOI: 10.21228/M89D8V This work is supported by NIH grant, U2C- DK119886.

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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.

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Study IDST002228
Study TitleEstrogen receptor a deficiency in cardiac myocytes reprograms heart-derived extracellular vesicle proteome and induces obesity in female mice (Part 2)
Study SummaryDysregulation of ERα has been linked with increased metabolic and cardiovascular disease risk. Uncovering the impact of ERα deficiency in specific tissues has implications for understanding the role of ERα in normal physiology and disease, the increased disease risk in postmenopausal women, and the design of tissue-specific ERα-based therapies for a range of pathologies including cardiac disease and cancer. Cardiac myocyte-specific ER knockout mice (ERαHKO) were generated to assess the role of ERα in the heart. Female ERαHKO mice displayed a modest cardiac phenotype, but unexpectedly, the most striking phenotype was obesity in female ERαHKO but not male ERHKO mice. In female ERαHKO mice we identified cardiac dysfunction, mild glucose and insulin intolerance, and reduced ERα gene expression in skeletal muscle and white adipose tissue (WAT). Gene expression, protein, lipidomic and metabolomic analyses showed evidence of contractile and/or metabolic dysregulation in heart, skeletal muscle and WAT. We also show that extracellular vesicles (EVs) collected from the perfusate of isolated hearts from female ERαHKO mice have a distinct proteome, and these EVs have the capacity to reprogram the proteome of a skeletal muscle cell including proteins linked with ERα, fatty acid regulation, lipid metabolism and mitochondrial function. This study uncovers a cardiac-initiated and sex-specific cardiometabolic phenotype that is regulated by ERα.
Institute
Baker Heart and Diabetes Institute
DepartmentDiscovery and Preclinical Science
LaboratoryCardiac Hypertrophy
Last NameTham
First NameYow Keat
Address75 Commercial Rd, Melbourne, Victoria, 3004, Australia
Emailyowkeat.tham@baker.edu.au
Phone0385321266
Submit Date2022-07-17
Raw Data AvailableYes
Raw Data File Type(s)qgd
Analysis Type DetailGC-MS
Release Date2023-01-02
Release Version1
Yow Keat Tham Yow Keat Tham
https://dx.doi.org/10.21228/M89D8V
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:

Project:

Project ID:PR001419
Project DOI:doi: 10.21228/M89D8V
Project Title:Estrogen receptor α deficiency in cardiac myocytes reprograms heart-derived extracellular vesicle proteome and induces obesity in female mice
Project Summary:Tissues (ventricles, skeletal muscles-soleus, subcutaneous fat) from male and female ERalpha cardiac-specific knockout and floxed control aged mice (54-59 weeks old, male FC n=5, male KO n=5, female FC n=8, female KO n=7 ) were subjected to metabolomic profiling.
Institute:Baker Heart and Diabetes Institute
Department:Discovery and Preclinical Science
Laboratory:Cardiac Hypertrophy
Last Name:Tham
First Name:Yow Keat
Address:75 Commercial Rd, Melbourne, Victoria, 3004, Australia
Email:yowkeat.tham@baker.edu.au
Phone:0385321266
Publications:https://www.nature.com/articles/s44161-023-00223-z

Subject:

Subject ID:SU002314
Subject Type:Mammal
Subject Species:Mus musculus
Taxonomy ID:10090
Genotype Strain:C57BL6 and FVB mixed strain
Age Or Age Range:54-59 weeks old
Gender:Male and female
Animal Feed:Specialty Feeds Irradiated Rat and Mouse Standard Chow Diet

Factors:

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

mb_sample_id local_sample_id Sex Genotype
SA21235537910_HFemale ERalpha-knockout
SA21235637914_HFemale ERalpha-knockout
SA21235737917_HFemale ERalpha-knockout
SA21235837906_HFemale ERalpha-knockout
SA21235937905_HFemale ERalpha-knockout
SA21236037915_HFemale ERalpha-knockout
SA21236137910_SkFemale ERalpha-knockout
SA21236237905_SkFemale ERalpha-knockout
SA21236337899_SkFemale ERalpha-knockout
SA21236437906_SkFemale ERalpha-knockout
SA21236537917_SkFemale ERalpha-knockout
SA21236637899_HFemale ERalpha-knockout
SA21236737914_SkFemale ERalpha-knockout
SA21236837915_SkFemale ERalpha-knockout
SA21236937910_subFemale ERalpha-knockout
SA21237037906_subFemale ERalpha-knockout
SA21237137914_subFemale ERalpha-knockout
SA21237237915_subFemale ERalpha-knockout
SA21237337917_subFemale ERalpha-knockout
SA21237437899_subFemale ERalpha-knockout
SA21237537905_subFemale ERalpha-knockout
SA21237637913_SkFemale Floxed Control
SA21237737890_subFemale Floxed Control
SA21237837912_SkFemale Floxed Control
SA21237937916_SkFemale Floxed Control
SA21238037896_SkFemale Floxed Control
SA21238137909_SkFemale Floxed Control
SA21238237891_SkFemale Floxed Control
SA21238337893_subFemale Floxed Control
SA21238437916_subFemale Floxed Control
SA21238537913_subFemale Floxed Control
SA21238637891_subFemale Floxed Control
SA21238737909_subFemale Floxed Control
SA21238837896_subFemale Floxed Control
SA21238937912_subFemale Floxed Control
SA21239037893_SkFemale Floxed Control
SA21239137896_HFemale Floxed Control
SA21239237893_HFemale Floxed Control
SA21239337909_HFemale Floxed Control
SA21239437913_HFemale Floxed Control
SA21239537912_HFemale Floxed Control
SA21239637916_HFemale Floxed Control
SA21239737890_HFemale Floxed Control
SA21239837891_HFemale Floxed Control
SA21239937890_SkFemale Floxed Control
SA21240037908_subMale ERalpha-knockout
SA21240137904_subMale ERalpha-knockout
SA21240237902_subMale ERalpha-knockout
SA21240337898_HMale ERalpha-knockout
SA21240437901_HMale ERalpha-knockout
SA21240537908_HMale ERalpha-knockout
SA21240637904_HMale ERalpha-knockout
SA21240737902_HMale ERalpha-knockout
SA21240837898_subMale ERalpha-knockout
SA21240937901_subMale ERalpha-knockout
SA21241037904_SkMale ERalpha-knockout
SA21241137902_SkMale ERalpha-knockout
SA21241237901_SkMale ERalpha-knockout
SA21241337898_SkMale ERalpha-knockout
SA21241437908_SkMale ERalpha-knockout
SA21241537907_HMale Floxed Control
SA21241637895_HMale Floxed Control
SA21241737897_HMale Floxed Control
SA21241837900_HMale Floxed Control
SA21241937907_SkMale Floxed Control
SA21242037900_SkMale Floxed Control
SA21242137897_subMale Floxed Control
SA21242237900_subMale Floxed Control
SA21242337907_subMale Floxed Control
SA21242437895_subMale Floxed Control
SA21242537894_subMale Floxed Control
SA21242637897_SkMale Floxed Control
SA21242737895_SkMale Floxed Control
SA21242837894_SkMale Floxed Control
SA21242937894_HMale Floxed Control
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Collection:

Collection ID:CO002307
Collection Summary:Ventricles were dissected from mice such that each sample will include left and right ventricular tissue.Tissues were snap frozen in liquid nitrogen and stored in -80 freezer until tissues were processed for metabolomics.
Sample Type:Ventricles, Skeletal Muscles, Subcutaneous fat
Storage Conditions:-80℃

Treatment:

Treatment ID:TR002326
Treatment Summary:Mice did not undergo specific treatment, as this was a basal phenotyping study. Mice were fasted for 6 hours before dissections, and a lethal dose of anesthesia was delivered via intraperitoneal injection before tissue collection.
Animal Anesthesia:Pentobarbitone
Animal Fasting:6 hours

Sample Preparation:

Sampleprep ID:SP002320
Sampleprep Summary:600 µL of 3:1 methanol/water (containing 13C6 Sorbitol & 13C5, 15N Valine as internal standards) was added to the samples and cryomilled for 45 sec x 3 at 6800 rpm. 480 µL of the homogenate was transferred into a fresh tube and centrifuged for 10 min at 12700 rpm. 100 µL of the supernatant of each sample was pooled to make up the pooled biological quality controls (PBQCs). 100 µL of each sample (study samples & PBQCs) was dried using a SpeedVac vacuum concentrator prior to derivatization. The samples and PBQCs were methoximated (methoxyamine hydrochloride - 25 µL) and trimethylsilylated (BSTFA - 25 µL) to enable gas phase analysis.

Combined analysis:

Analysis ID AN003637
Analysis type MS
Chromatography type GC
Chromatography system Shimadzu Nexis GC-2030
Column Agilent DB5-MS (30m x 0.25mm, 0.25um)
MS Type EI
MS instrument type Triple quadrupole
MS instrument name Shimadzu TQ8050 NX
Ion Mode POSITIVE
Units abundance

Chromatography:

Chromatography ID:CH002692
Chromatography Summary:The GC-MS system used comprised of an AOC6000 autosampler, a 2030 Shimadzu gas chromatograph and a TQ8050NX triple quadrupole mass spectrometer (Shimadzu, Japan). The mass spectrometer was tuned according to the manufacturer’s recommendations using tris-(perfluorobutyl)-amine (CF43). GC-MS was performed on a 30m Agilent DB-5 column with 0.25mm internal diameter column and 1µm film thickness. The injection temperature (inlet) was set at 280°C, the MS transfer line at 280°C and the ion source adjusted to 200°C. Helium was used as the carrier gas at a flow rate of 1 mL/min and argon gas was used in the collision cell to generate the MRM product ion. The analysis of TMS samples was performed under the following oven temperature program; 100°C start temperature, hold for 4 minutes, followed by a 10°C min-1 oven temperature ramp to 320°C with a following final hold for 11 minutes. Approximately 520 targets were collected using the Shimadzu Smart Metabolite Database, where each target comprised a quantifier MRM along with a qualifier MRM, which covers approximately 350 endogenous metabolites and multiple stable isotopically labelled internal standards. Resultant data was processed using Shimadzu LabSolutions Insight software, where peak integrations were visually validated and manually corrected where required.
Instrument Name:Shimadzu Nexis GC-2030
Column Name:Agilent DB5-MS (30m x 0.25mm, 0.25um)
Chromatography Type:GC

MS:

MS ID:MS003388
Analysis ID:AN003637
Instrument Name:Shimadzu TQ8050 NX
Instrument Type:Triple quadrupole
MS Type:EI
MS Comments:The GC-MS system used comprised of an AOC6000 autosampler, a 2030 Shimadzu gas chromatograph and a TQ8050NX triple quadrupole mass spectrometer (Shimadzu, Japan). The mass spectrometer was tuned according to the manufacturer’s recommendations using tris-(perfluorobutyl)-amine (CF43). GC-MS was performed on a 30m Agilent DB-5 column with 0.25mm internal diameter column and 1µm film thickness. The injection temperature (inlet) was set at 280°C, the MS transfer line at 280°C and the ion source adjusted to 200°C. Helium was used as the carrier gas at a flow rate of 1 mL/min and argon gas was used in the collision cell to generate the MRM product ion. The analysis of TMS samples was performed under the following oven temperature program; 100°C start temperature, hold for 4 minutes, followed by a 10°C min-1 oven temperature ramp to 320°C with a following final hold for 11 minutes. Approximately 520 targets were collected using the Shimadzu Smart Metabolite Database, where each target comprised a quantifier MRM along with a qualifier MRM, which covers approximately 350 endogenous metabolites and multiple stable isotopically labelled internal standards. Resultant data was processed using Shimadzu LabSolutions Insight software, where peak integrations were visually validated and manually corrected where required.
Ion Mode:POSITIVE
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