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.

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	ST002228
Study Title	Estrogen receptor a deficiency in cardiac myocytes reprograms heart-derived extracellular vesicle proteome and induces obesity in female mice (Part 2)
Study Summary	Dysregulation 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
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
Submit Date	2022-07-17
Raw Data Available	Yes
Raw Data File Type(s)	qgd
Analysis Type Detail	GC-MS
Release Date	2023-01-02
Release Version	1

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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.

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.