Summary of Study ST002229

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.

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.

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Study IDST002229
Study TitleEstrogen receptor α deficiency in cardiac myocytes reprograms heart-derived extracellular vesicle proteome and induces obesity in female mice (Part 1)
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 ERαHKO 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
Last NameTham
First NameYow Keat
Address75 Commercial Rd, Melbourne, Victoria, 3004, Australia
Emailyowkeat.tham@baker.edu.au
Phone+65385321266
Submit Date2022-05-18
Num Groups4
Total Subjects25
Num Males10
Num Females15
Raw Data AvailableYes
Raw Data File Type(s)d
Analysis Type DetailLC-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

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Factors:

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

mb_sample_id local_sample_id Sex Genotype
SA21243037899_LivFemale ERalpha-knockout
SA21243137915_SkFemale ERalpha-knockout
SA21243237910_SkFemale ERalpha-knockout
SA21243337906_LivFemale ERalpha-knockout
SA21243437914_SkFemale ERalpha-knockout
SA21243537917_LivFemale ERalpha-knockout
SA21243637914_HFemale ERalpha-knockout
SA21243737915_HFemale ERalpha-knockout
SA21243837910_LivFemale ERalpha-knockout
SA21243937917_SkFemale ERalpha-knockout
SA21244037899 _PFemale ERalpha-knockout
SA21244137914 _PFemale ERalpha-knockout
SA21244237915 _PFemale ERalpha-knockout
SA21244337905_SkFemale ERalpha-knockout
SA21244437899_SkFemale ERalpha-knockout
SA21244537910 _PFemale ERalpha-knockout
SA21244637917 _PFemale ERalpha-knockout
SA21244737910_HFemale ERalpha-knockout
SA21244837905 _PFemale ERalpha-knockout
SA21244937906 _PFemale ERalpha-knockout
SA21245037906_SkFemale ERalpha-knockout
SA21245137905_LivFemale ERalpha-knockout
SA21245237905_epiFemale ERalpha-knockout
SA21245337917_HFemale ERalpha-knockout
SA21245437906_epiFemale ERalpha-knockout
SA21245537910_epiFemale ERalpha-knockout
SA21245637915_epiFemale ERalpha-knockout
SA21245737899_epiFemale ERalpha-knockout
SA21245837915_LivFemale ERalpha-knockout
SA21245937905_HFemale ERalpha-knockout
SA21246037906_HFemale ERalpha-knockout
SA21246137899_HFemale ERalpha-knockout
SA21246237914_LivFemale ERalpha-knockout
SA21246337914_epiFemale ERalpha-knockout
SA21246437913_epiFemale Floxed Control
SA21246537916_SkFemale Floxed Control
SA21246637896_SkFemale Floxed Control
SA21246737891_SkFemale Floxed Control
SA21246837909_SkFemale Floxed Control
SA21246937912_epiFemale Floxed Control
SA21247037912_SkFemale Floxed Control
SA21247137913_SkFemale Floxed Control
SA21247237893_epiFemale Floxed Control
SA21247337909_LivFemale Floxed Control
SA21247437896_LivFemale Floxed Control
SA21247537916_LivFemale Floxed Control
SA21247637912_LivFemale Floxed Control
SA21247737890_SkFemale Floxed Control
SA21247837913_LivFemale Floxed Control
SA21247937893_LivFemale Floxed Control
SA21248037891_LivFemale Floxed Control
SA21248137896_epiFemale Floxed Control
SA21248237909_epiFemale Floxed Control
SA21248337891_epiFemale Floxed Control
SA21248437890_epiFemale Floxed Control
SA21248537890_LivFemale Floxed Control
SA21248637916_epiFemale Floxed Control
SA21248737893_SkFemale Floxed Control
SA21248837916_HFemale Floxed Control
SA21248937896 _PFemale Floxed Control
SA21249037916 _PFemale Floxed Control
SA21249137912 _PFemale Floxed Control
SA21249237912_HFemale Floxed Control
SA21249337913_HFemale Floxed Control
SA21249437890 _PFemale Floxed Control
SA21249537891 _PFemale Floxed Control
SA21249637893 _PFemale Floxed Control
SA21249737913 _PFemale Floxed Control
SA21249837909 _PFemale Floxed Control
SA21249937909_HFemale Floxed Control
SA21250037891_HFemale Floxed Control
SA21250137890_HFemale Floxed Control
SA21250237896_HFemale Floxed Control
SA21250337893_HFemale Floxed Control
SA21250437908_SkMale ERalpha-knockout
SA21250537898 _PMale ERalpha-knockout
SA21250637902_HMale ERalpha-knockout
SA21250737901_HMale ERalpha-knockout
SA21250837904_HMale ERalpha-knockout
SA21250937898_HMale ERalpha-knockout
SA21251037902 _PMale ERalpha-knockout
SA21251137901_epiMale ERalpha-knockout
SA21251237908_epiMale ERalpha-knockout
SA21251337904 _PMale ERalpha-knockout
SA21251437904_epiMale ERalpha-knockout
SA21251537902_epiMale ERalpha-knockout
SA21251637898_epiMale ERalpha-knockout
SA21251737908_HMale ERalpha-knockout
SA21251837901 _PMale ERalpha-knockout
SA21251937902_SkMale ERalpha-knockout
SA21252037902_LivMale ERalpha-knockout
SA21252137901_SkMale ERalpha-knockout
SA21252237898_SkMale ERalpha-knockout
SA21252337908 _PMale ERalpha-knockout
SA21252437898_LivMale ERalpha-knockout
SA21252537904_SkMale ERalpha-knockout
SA21252637901_LivMale ERalpha-knockout
SA21252737908_LivMale ERalpha-knockout
SA21252837904_LivMale ERalpha-knockout
SA21252937900_SkMale Floxed Control
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