Conditional PPARγ knockout from cardiomyocytes of adult mice impairs myocardial fatty acid utilization and cardiac function.

Abstract

While the roles of PPARα and PPARδ (β) in transcriptional regulation of myocardial lipid metabolisms are well established, an essential role of PPARγ in regulating lipid metabolisms in the adult heart remains unclear. In this study, we investigated whether PPARγ is required for normal myocardial lipid metabolism at basal condition in adult mice. We assessed the short-term cardiomyocyte-restricted PPARγ knockout mice with a Tamoxifen inducible Cre-LoxP mediated gene targeting strategy. The expression of PPARγ mRNA and protein in cardiomyocytes of adult mice was substantially reduced after short-term induction. Transcript and protein levels of important proteins in fatty acid uptake and oxidation, such as CD36, heart type-fatty acid binding protein (FABP), and carnitine palmitoyltransferase I (CPT-I) were reduced in the PPARγ deficient hearts. Myocardial fatty acid utilization and cardiac contraction were depressed in PPARγ deficient hearts. The PPARγ deficient hearts exhibited modest cardiac hypertrophy compared with controls. These results indicate that PPARγ is a transcription factor that is required for basal myocardial fatty acid utilization in the adult heart.