Abstract
Abstract 328: Med13 regulates cardiac metabolism
Circulation research, Vol.113(suppl_1)
08/2013
DOI: 10.1161/res.113.suppl_1.A328
Abstract
Background:
The heart is a metabolic organ that primarily utilizes fatty acids as energy substrate. While it is well established that the heart is metabolically flexible, the transcriptional network regulating cardiac metabolism is only partially understood. We have previously demonstrated that cardiac overexpression of Med13, a component of the Mediator Complex that regulates transcription, results in a lean phenotype with enhanced basal metabolic rates. We now investigate the mechanisms contributing to metabolic changes in mice with cardiac over-expression of Med13(Med13cTg).
Methods and Results:
Cardiac fludeoxyglucose (18F-FDG)-PET imaging analysis revealed that Med13cTg hearts take up more glucose than wild type littermates. To determine pathways responsible for enhanced glucose uptake, ventricles from Med13cTg mice were subjected to RNA-seq and metabolomic analysis. The expression of fatty acid oxidation genes was decreased in Med13cTg hearts, accompanied by an increase in acyl CoA and a decrease in acetyl CoA. These data suggest that beta oxidation is decreased in Med13cTg hearts. Mitochondria function was therefore determined in Med13cTg hearts by performing electron-flow analyses and assessing oxygen consumption rates. Indeed, oxygen consumption rates were decreased in mitochondria isolated from Med13cTg hearts. Expression of Krebs Cycle genes and corresponding intermediary metabolites were also decreased in Med13cTg hearts, suggesting decreased flux through this pathway as well.
Conclusions:
Overexpression of Med13 in the heart increases glucose uptake and decreases fatty acid oxidation in the heart. We speculate that Med13 transcriptionally regulates key mediators of cardiac metabolism. The mechanisms by which this occurs are currently under investigation.
Details
- Title: Subtitle
- Abstract 328: Med13 regulates cardiac metabolism
- Creators
- Kedryn K Baskin - UT Southwestern Med Cntr, Dallas, TXChad E Grueter - University of IowaChristine M Kusminski - UT Southwestern Med Cntr, Dallas, TXPhilipp E Scherer - UT Southwestern Med Cntr, Dallas, TXRhonda Bassel-Duby - UT Southwestern Med Cntr, Dallas, TXEric N Olson - UT Southwestern Med Cntr, Dallas, TX
- Resource Type
- Abstract
- Publication Details
- Circulation research, Vol.113(suppl_1)
- DOI
- 10.1161/res.113.suppl_1.A328
- ISSN
- 0009-7330
- eISSN
- 1524-4571
- Language
- English
- Date published
- 08/2013
- Academic Unit
- Cardiovascular Medicine; Craniofacial Anomalies Research Center; Internal Medicine
- Record Identifier
- 9984362350402771
Metrics
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