Journal article
A Cardiac MicroRNA Governs Systemic Energy Homeostasis by Regulation of MED13
Cell, Vol.149(3), pp.671-683
04/27/2012
DOI: 10.1016/j.cell.2012.03.029
PMCID: PMC3340581
PMID: 22541436
Abstract
Obesity, type 2 diabetes, and heart failure are associated with aberrant cardiac metabolism. We show that the heart regulates systemic energy homeostasis via MED13, a subunit of the Mediator complex, which controls transcription by thyroid hormone and other nuclear hormone receptors. MED13, in turn, is negatively regulated by a heart-specific microRNA, miR-208a. Cardiac-specific overexpression of MED13 or pharmacologic inhibition of miR-208a in mice confers resistance to high-fat diet-induced obesity and improves systemic insulin sensitivity and glucose tolerance. Conversely, genetic deletion of MED13 specifically in cardiomyocytes enhances obesity in response to high-fat diet and exacerbates metabolic syndrome. The metabolic actions of MED13 result from increased energy expenditure and regulation of numerous genes involved in energy balance in the heart. These findings reveal a role of the heart in systemic metabolic control and point to MED13 and miR-208a as potential therapeutic targets for metabolic disorders.
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▸ Pharmacologic inhibition of miR-208a confers resistance to diet-induced obesity ▸ Cardiac expression of MED13 enhances whole-body metabolism ▸ MED13 and miR-208a counterregulate a metabolic gene program in the heart ▸ The heart can regulate global metabolic homeostasis
miR-208a regulates cardiac levels of a subunit of the Mediator complex, controlling transcription by nuclear hormone receptors. Disruption of this regulation alters whole-body energy homeostasis, revealing a role for the heart in systemic metabolic control.
Details
- Title: Subtitle
- A Cardiac MicroRNA Governs Systemic Energy Homeostasis by Regulation of MED13
- Creators
- Chad E Grueter - Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USAEva van Rooij - miRagen Therapeutics, Inc., Boulder, CO 80301, USABrett A Johnson - Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USASusan M DeLeon - Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USALillian B Sutherland - Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USAXiaoxia Qi - Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USALaurent Gautron - Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USAJoel K Elmquist - Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USARhonda Bassel-Duby - Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USAEric N Olson - Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
- Resource Type
- Journal article
- Publication Details
- Cell, Vol.149(3), pp.671-683
- DOI
- 10.1016/j.cell.2012.03.029
- PMID
- 22541436
- PMCID
- PMC3340581
- NLM abbreviation
- Cell
- ISSN
- 0092-8674
- eISSN
- 1097-4172
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 04/27/2012
- Academic Unit
- Cardiovascular Medicine; Craniofacial Anomalies Research Center; Internal Medicine
- Record Identifier
- 9984094598502771
Metrics
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