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A cardiac microRNA governs systemic energy homeostasis by regulation of MED13.

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.

Pubmed ID: 22541436

Authors

  • Grueter CE
  • van Rooij E
  • Johnson BA
  • DeLeon SM
  • Sutherland LB
  • Qi X
  • Gautron L
  • Elmquist JK
  • Bassel-Duby R
  • Olson EN

Journal

Cell

Publication Data

April 27, 2012

Associated Grants

  • Agency: NIDDK NIH HHS, Id: PL1 DK081182
  • Agency: NIAMS NIH HHS, Id: R01 AR040339
  • Agency: NIAMS NIH HHS, Id: R01 AR040339-11
  • Agency: NIAMS NIH HHS, Id: R01 AR040339-11S1
  • Agency: NHLBI NIH HHS, Id: R01 HL053351
  • Agency: NHLBI NIH HHS, Id: R01 HL053351-05
  • Agency: NHLBI NIH HHS, Id: R01 HL061544
  • Agency: NHLBI NIH HHS, Id: R01 HL061544-04
  • Agency: NHLBI NIH HHS, Id: R01 HL061544-05
  • Agency: NHLBI NIH HHS, Id: R01 HL077439
  • Agency: NHLBI NIH HHS, Id: R01 HL077439-09
  • Agency: NHLBI NIH HHS, Id: R01 HL077439-10
  • Agency: NHLBI NIH HHS, Id: R01 HL083371
  • Agency: NHLBI NIH HHS, Id: R01 HL083371-04
  • Agency: NHLBI NIH HHS, Id: R01 HL083371-04W1
  • Agency: NHLBI NIH HHS, Id: R01 HL083371-05
  • Agency: NHLBI NIH HHS, Id: R01 HL093039
  • Agency: NHLBI NIH HHS, Id: R01 HL093039-03S1
  • Agency: NHLBI NIH HHS, Id: R01 HL111665
  • Agency: NHLBI NIH HHS, Id: R01 HL111665-02
  • Agency: NHLBI NIH HHS, Id: R37 HL053351
  • Agency: NHLBI NIH HHS, Id: R37 HL053351-14
  • Agency: NHLBI NIH HHS, Id: R37 HL053351-15
  • Agency: NIDDK NIH HHS, Id: RL1DK081185
  • Agency: NCRR NIH HHS, Id: UL1 RR024923

Mesh Terms

  • Animals
  • Diabetes Mellitus, Type 2
  • Energy Metabolism
  • Female
  • Glucose
  • Heart
  • Homeostasis
  • Humans
  • Insulin Resistance
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • MicroRNAs
  • Myocardium
  • Obesity