title: MED13-dependent signaling from the heart confers leanness by enhancing metabolism in adipose tissue and liver.
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.
authors.affiliation: Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Kedryn K
authors.initials: KK
authors.lastname: Baskin
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA, USA.
authors.forename: Chad E
authors.initials: CE
authors.lastname: Grueter
authors.affiliation: Touchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Kusminski
authors.affiliation: Touchstone Diabetes Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: William L
authors.initials: WL
authors.lastname: Holland
authors.affiliation: Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Angie L
authors.initials: AL
authors.lastname: Bookout
authors.affiliation: 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.
authors.forename: Santosh
authors.initials: S
authors.lastname: Satapati
authors.affiliation: Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Y Megan
authors.initials: YM
authors.lastname: Kong
authors.affiliation: 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.
authors.forename: Shawn C
authors.initials: SC
authors.lastname: Burgess
authors.affiliation: 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, USA.
authors.forename: Craig R
authors.initials: CR
authors.lastname: Malloy
authors.affiliation: 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, USA.
authors.forename: Philipp E
authors.initials: PE
authors.lastname: Scherer
authors.affiliation: 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, USA.
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Newgard
authors.affiliation: Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX, USA Hamon Center for Regenerative Science and Medicine, Dallas, TX, USA.
authors.forename: Rhonda
authors.initials: R
authors.lastname: Bassel-Duby
authors.affiliation: 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.
authors.forename: Eric N
authors.initials: EN
authors.lastname: Olson
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D052436:Adipose Tissue, White / Q000378:metabolism*; D000818:Animals; D004734:Energy Metabolism; D005260:Female; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008297:Male; D056892:Mediator Complex / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008928:Mitochondria / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D015398:Signal Transduction; D013851:Thinness / Q000235:genetics / Q000378:metabolism*
chemical_list: C488666:MED13 protein, human; D056892:Mediator Complex
keywords: energy homeostasis; mediator complex; metabolic flexibility; metabolic gene expression; metabolism