Saturated fats found in high-fat diets increase the risk of heart failure. Now, Manisha Gupte, PhD, Hind Lal, PhD, and colleagues show that the presence of an enzyme called GSK-3beta in the heart is crucial to protect against obesity-related cardiac dysfunction.

To better understand the role of GSK-3beta, the scientists generated mice in which the gene for the enzyme was “knocked out” in heart cells. When fed a high-fat diet, the knockout mice developed severe heart disease compared to normal controls even though there was no difference in obesity.

On a normal diet, the related enzyme, GSK-3alpha, compensated for the absence of GSK-3beta in the knockout mice. On a high-fat diet, however, this protection was lost. The absence of GSK-3beta led to excessive accumulation of beta-catenin, a signaling molecule associated with heart abnormalities.

These findings, published recently in the International Journal of Cardiology, point to the potential adverse cardiac consequences of chronic GSK-3 inhibition.