Nature Medicine10, 1245 - 1250 (2004)
Published online: 10 October 2004; | doi:10.1038/nm1116
Cardiomyocyte-restricted peroxisome proliferator-activated receptor- deletion perturbs myocardial fatty acid oxidation and leads to cardiomyopathy
Lihong Cheng1, Guoliang Ding1, Qianhong Qin1, Yao Huang1, William Lewis2, Nu He3, Ronald M Evans4, Michael D Schneider5, Florence A Brako1, Yan Xiao1, Yuqing E Chen1
& Qinglin Yang1
1
Cardiovascular Research Institute, Morehouse School of Medicine, Atlanta, Georgia 30310, USA.
2
Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia 30322, USA.
3
Department of Pharmacology, Morehouse School of Medicine, Atlanta, Georgia 30310, USA.
4
Howard Hughes Medical Institute, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.
5
Center for Cardiovascular Development, Baylor College of Medicine, Houston, Texas 77030, USA.
Correspondence should be addressed to Qinglin Yang qyang@msm.edu
Fatty acid oxidation (FAO) is a primary energy source for meeting the heart's energy requirements1,
2,
3. Peroxisome proliferator-activated receptor- (PPAR-) may have important roles in FAO4,
5,
6,
7,
8. But it remains unclear whether PPAR- is required for maintaining basal myocardial FAO. We show that cre-loxP-mediated cardiomyocyte-restricted deletion of PPAR- in mice downregulates constitutive expression of key FAO genes and decreases basal myocardial FAO. These mice have cardiac dysfunction, progressive myocardial lipid accumulation, cardiac hypertrophy and congestive heart failure with reduced survival. Thus, chronic myocardial PPAR- deficiency leads to lipotoxic cardiomyopathy. Together, our data show that PPAR- is a crucial determinant of constitutive myocardial FAO and is necessary to maintain energy balance and normal cardiac function. We suggest that PPAR- is a potential therapeutic target in treating lipotoxic cardiomyopathy and other heart diseases.
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deletion perturbs myocardial fatty acid oxidation and leads to cardiomyopathy
(PPAR-
