Original Article Conditional PPARgamma knockout from cardiomyocytes of adult mice disturbs myocardial fatty acid utilization
Jinwen Luo, Sijie Wu, Jian Liu, Yuquan Li, Huan Yang, Teayoun Kim, Olga Zhelyabovska, Guoliang Ding, Yiqun Zhou, Yifeng Yang and Qinglin Yang
Department of Nutrition Sciences, University of Alabama at Birmingham, 1675 University Blvd, Birmingham, AL, USA; Department of Cardio-thoracic Surgery, The Xiangya Medical College, Zhongnan University, Changsha, China; Department of Anatamy, The Second Milatary Medical University, Shanghai, China; Department of Pediatrics, Emory University, Atlanta, GA, USA
Received September 23, 2010; accepted September 30, 2010; October 1, 2010; Published January 1, 2011
Abstract: While the roles of PPARalpha and PPARdelta (beta) in transcriptional regulation of myocardial lipid metabolisms are well established, an essential role of PPARgamma in regulating lipid metabolisms in the adult heart remains unclear. In this study, we investigate whether PPARgamma is required for normal myocardial lipid metabolism at basal condition in adult mice. We assessed the short-term cardiomyocyte-restricted PPARgamma knockout mice with a Tamoxifen inducible Cre-LoxP mediated gene targeting strategy. The expression of PPARgamma 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 PPARgamma deficient hearts. Myocardial fatty acid utilization and cardiac contraction was depressed in PPARgamma deficient hearts. The PPARgamma deficient hearts exhibited modest cardiac hypertrophy compared with controls. These results indicate that PPARgamma is a transcription factor that is required for basal myocardial fatty acid utilization in the adult heart. (AJTR1009002).
Address all correspondence to: Qinglin Yang, MD, PhD Department of Nutrition Sciences University of Alabama at Birmingham 1675 University Blvd Birmingham, AL 35294-3360, USA. E-mail: qyang@uab.edu