@article{7434b3fa79c044e5bb5918a5938a06e2,
title = "A cardiac MicroRNA governs systemic energy homeostasis by regulation of MED13",
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. PaperClip:",
author = "Grueter, {Chad E.} and {Van Rooij}, Eva and Johnson, {Brett A.} and Deleon, {Susan M.} and Sutherland, {Lillian B.} and Xiaoxia Qi and Laurent Gautron and Elmquist, {Joel K.} and Rhonda Bassel-Duby and Olson, {Eric N.}",
note = "Funding Information: We thank Carrie A. Grueter, Jose Cabrera, John McAnally, Evelyn Tennison, and Jennifer Brown for their assistance. We appreciate the services of the UT Southwestern Mouse Metabolic Phenotyping Core, supported by National Institute of Health Grants PL1 DK081182 and UL1 RR024923, and the UT Southwestern Transgenic Core Facility. We thank James Richardson and the histology group for their assistance. This work was supported, in part, by grants from National Institutes of Health, the Donald W. Reynolds Center for Clinical Cardiovascular Research, the Robert A. Welch Foundation (grant I-0025), the Fondation Leducq-Transatlantic of Excellence in Cardiovascular Research Program, and the American Heart Association-Jon Holden DeHaan Foundation to E.N.O. C.E.G. was supported by a fellowship from the American Diabetes Association (7-09-CVD-04). J.K.E. was supported by RL1DK081185. E.N.O. and E.v.R. are cofounders of miRagen Therapeutics, a company focused on developing miRNA-based therapies for cardiovascular disease. ",
year = "2012",
month = apr,
day = "27",
doi = "10.1016/j.cell.2012.03.029",
language = "English (US)",
volume = "149",
pages = "671--683",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "3",
}