12 research outputs found
Cardiomyocyte expression of PPARγ leads to cardiac dysfunction in mice
Three forms of PPARs are expressed in the heart. In animal models,
PPARγ agonist treatment improves lipotoxic cardiomyopathy; however,
PPARγ agonist treatment of humans is associated with peripheral
edema and increased heart failure. To directly assess effects of increased
PPARγ on heart function, we created transgenic mice expressing
PPARγ1 in the heart via the cardiac α–myosin
heavy chain (α-MHC) promoter. PPARγ1-transgenic mice had
increased cardiac expression of fatty acid oxidation genes and increased
lipoprotein triglyceride (TG) uptake. Unlike in cardiac
PPARα-transgenic mice, heart glucose transporter 4 (GLUT4) mRNA
expression and glucose uptake were not decreased. PPARγ1-transgenic
mice developed a dilated cardiomyopathy associated with increased lipid and
glycogen stores, distorted architecture of the mitochondrial inner matrix, and
disrupted cristae. Thus, while PPARγ agonists appear to have
multiple beneficial effects, their direct actions on the myocardium have the
potential to lead to deterioration in heart function