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 ERHKO 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 |
| 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 |
Select appropriate tab below to view additional metadata details:
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 TQ8050NX |
| Ion Mode | POSITIVE |
| Units | abundance |
MS:
| MS ID: | MS003388 |
| Analysis ID: | AN003637 |
| Instrument Name: | Shimadzu TQ8050NX |
| 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 |
