Drugs that are agonists of the receptor PPAR-gamma are used to treat individuals with diabetes. However, it has been suggested that their use is associated with a slightly increased risk of heart failure. In a new study, Ira Goldberg and colleagues at Columbia University, New York, outline a potential explanation for the adverse effects observed in a minority of patients being treated with PPAR-gamma agonists.
To directly determine the effects of increased PPAR-gamma activity in the heart, the authors generated mice expressing increased amounts of PPAR-gamma in the heart compared with normal mice. Fat and carbohydrates accumulated in the heart muscle cells of these mice causing a deterioration in heart function (a process known as glucolipotoxicity). Administration of a PPAR-gamma agonist to these mice exacerbated their heart dysfunction. The authors therefore conclude that the adverse effect of PPAR-gamma agonists on heart function in humans might be due to glucolipotoxocity.
TITLE: Cardiomyocyte expression of PPAR-gamma leads to cardiac dysfunction in mice
AUTHOR CONTACT:
Ira J. Goldberg
Columbia University, New York, New York, USA.
Phone: (212) 305-5961; Fax: (212) 305-5384; E-mail: ijg3@columbia.edu .
View the PDF of this article at: https://www.the-jci.org/article.php?id=30335
Journal of Clinical Investigation