Journal article
MED13-dependent signaling from the heart confers leanness by enhancing metabolism in adipose tissue and liver
EMBO molecular medicine, Vol.6(12), pp.1610-1621
12/2014
DOI: 10.15252/emmm.201404218
PMCID: PMC4287978
PMID: 25422356
Abstract
The heart requires a continuous supply of energy but has little capacity for energy storage and thus relies on exogenous metabolic sources. We previously showed that cardiac MED13 modulates systemic energy homeostasis in mice. Here, we sought to define the extra-cardiac tissue(s) that respond to cardiac MED13 signaling. We show that cardiac overexpression of MED13 in transgenic (MED13cTg) mice confers a lean phenotype that is associated with increased lipid uptake, beta-oxidation and mitochondrial content in white adipose tissue (WAT) and liver. Cardiac expression of MED13 decreases metabolic gene expression in the heart but enhances them in WAT. Although exhibiting increased energy expenditure in the fed state, MED13cTg mice metabolically adapt to fasting. Furthermore, MED13cTg hearts oxidize fuel that is readily available, rendering them more efficient in the fed state. Parabiosis experiments in which circulations of wild-type and MED13cTg mice are joined, reveal that circulating factor(s) in MED13cTg mice promote enhanced metabolism and leanness. These findings demonstrate that MED13 acts within the heart to promote systemic energy expenditure in extra-cardiac energy depots and point to an unexplored metabolic communication system between the heart and other tissues.
Details
- Title: Subtitle
- MED13-dependent signaling from the heart confers leanness by enhancing metabolism in adipose tissue and liver
- Creators
- Kedryn K Baskin - Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX, USAChad E Grueter - Division of Cardiovascular Medicine, Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA, USAChristine M Kusminski - Touchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USAWilliam L Holland - Touchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USAAngie L Bookout - Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX, USASantosh Satapati - Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, USA Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX, USAY Megan Kong - Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX, USAShawn C Burgess - Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, USA Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX, USACraig R Malloy - Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, USA Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX, USA Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, USA Department of Molecular Biophysics, University of Texas Southwestern Medical Center, Dallas, TX, USAPhilipp E Scherer - Touchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX, USAChristopher B Newgard - Sarah W. Stedman Nutrition and Metabolism Center, Duke University, Durham, NC, USA Duke Molecular Physiology Institute, Duke University, Durham, NC, USA Department of Pharmacology and Cancer Biology, Department of Medicine, Duke University, Durham, NC, USARhonda Bassel-Duby - Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX, USA Hamon Center for Regenerative Science and Medicine, Dallas, TX, USAEric N Olson - Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX, USA Hamon Center for Regenerative Science and Medicine, Dallas, TX, USA eric.olson@utsouthwestern.edu
- Resource Type
- Journal article
- Publication Details
- EMBO molecular medicine, Vol.6(12), pp.1610-1621
- DOI
- 10.15252/emmm.201404218
- PMID
- 25422356
- PMCID
- PMC4287978
- NLM abbreviation
- EMBO Mol Med
- ISSN
- 1757-4676
- eISSN
- 1757-4684
- Grant note
- R01 DK078184 / NIDDK NIH HHS P01-DK-58398 / NIDDK NIH HHS R01 HL077439 / NHLBI NIH HHS P01 DK058398 / NIDDK NIH HHS R01 DK099653 / NIDDK NIH HHS HL-093039 / NHLBI NIH HHS R01 HL093039 / NHLBI NIH HHS HL-077439 / NHLBI NIH HHS U01-HL-100401 / NHLBI NIH HHS P41 EB015908 / NIBIB NIH HHS HL-111665 / NHLBI NIH HHS U01 HL100401 / NHLBI NIH HHS R01 HL111665 / NHLBI NIH HHS
- Language
- English
- Date published
- 12/2014
- Academic Unit
- Cardiovascular Medicine; Craniofacial Anomalies Research Center; Internal Medicine
- Record Identifier
- 9984094345502771
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