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.
| Study ID | ST002229 |
| Study Title | Estrogen receptor α deficiency in cardiac myocytes reprograms heart-derived extracellular vesicle proteome and induces obesity in female mice (Part 1) |
| 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 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 Name | Tham |
| First Name | Yow Keat |
| Address | 75 Commercial Rd, Melbourne, Victoria, 3004, Australia |
| yowkeat.tham@baker.edu.au | |
| Phone | +65385321266 |
| Submit Date | 2022-05-18 |
| Num Groups | 4 |
| Total Subjects | 25 |
| Num Males | 10 |
| Num Females | 15 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | d |
| Analysis Type Detail | LC-MS |
| Release Date | 2023-01-02 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Combined analysis:
| Analysis ID | AN003638 |
|---|---|
| Analysis type | MS |
| Chromatography type | Reversed phase |
| Chromatography system | Agilent 1290 Infinity II |
| Column | Agilent Zorbax Eclipse Plus C18 (100 x 2.1mm, 1.8 um) |
| MS Type | ESI |
| MS instrument type | Triple quadrupole |
| MS instrument name | Agilent 6490 QQQ |
| Ion Mode | POSITIVE |
| Units | pmol per mg (tissues) pmol per ml (plasma) |
Chromatography:
| Chromatography ID: | CH002693 |
| 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, 1.8 um) |
| 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: | 0.4mL/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 |
