Biomedicine

Mediating Metabolism

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Science  11 May 2012:
Vol. 336, Issue 6082, pp. 649
DOI: 10.1126/science.336.6082.649-b

Heart disease is a common complication of obesity-associated metabolic disorders such as type 2 diabetes, but the molecular mechanisms underlying this link are not fully understood. Much research has focused on the notion that specific metabolic aberrations such as lipid accumulation compromise the heart's structure and function. A new study suggests that the situation is more complex: Rather than simply being an organ targeted by metabolic dysfunction, the heart itself may regulate whole-body metabolism. Grueter et al. observed improved metabolic features in transgenic mice with cardiac-specific overexpression of MED13, a regulatory subunit of Mediator (a protein complex bridging transcription factors and RNA polymerase). These mice were resistant to diet-induced obesity and metabolic syndrome because of an increase in energy expenditure, and they showed altered expression of genes controlled by the thyroid hormone receptor. Interestingly, cardiac expression of MED13 is negatively regulated by miR-208a, a microRNA encoded by an intron of a cardiac-specific myosin gene. Pharmacological inhibition of miR-208a in wild-type mice on a high-fat diet slowed both weight gain and the development of glucose intolerance.

Cell 149, 671 (2012).

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