Heart failure is known to be associated with insulin resistance, but the underlying mechanisms have been unclear. Shimizu et al. used mouse models to investigate this link and uncovered an important role for p53-induced adipose tissue inflammation in the co-development of these conditions. Surgically induced heart failure in mice caused insulin resistance, which was accompanied by increased adipose tissue lipolysis and inflammation. When subjected to the same procedure, mice lacking p53 specifically in adipose tissue did not become insulin resistant, showed less adipose tissue inflammation and had better cardiac function. Subsequent studies suggest an underlying mechanism whereby heart failure triggers adrenergic activation, which increases lipolysis in adipose tissue; in turn, this results in the production of DNA-damaging reactive oxygen species that initiate a p53-mediated cascade producing proinflammatory cytokines that contribute to insulin resistance.

Shimizu I., Yoshida Y., Katsuno T., Tateno K., Okada S., Moriya J., Yokoyama M., Nojima A., Ito T., Zechner R., et al. (2012). p53-induced adipose tissue inflammation is critically involved in the development of insulin resistance in heart failure. Cell Metab. 15, 51– 64.
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Written by editorial staff. © 2012. Published by The Company of Biologists Ltd.
2012
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