title: Cardiomyocyte-Restricted Deletion of PPARβ/δ in PPARα-Null Mice Causes Impaired Mitochondrial Biogenesis and Defense, but No Further Depression of Myocardial Fatty Acid Oxidation.
abstract: It is well documented that PPARα and PPARβ/δ share overlapping functions in regulating myocardial lipid metabolism. However, previous studies demonstrated that cardiomyocyte-restricted PPARβ/δ deficiency in mice leads to severe cardiac pathological development, whereas global PPARα knockout shows a benign cardiac phenotype. It is unknown whether a PPARα-null background would alter the pathological development in mice with cardiomyocyte-restricted PPARβ/δ deficiency. In the present study, a mouse model with long-term PPARβ/δ deficiency in PPARα-null background showed a comparably reduced cardiac expression of lipid metabolism to those of single PPAR-deficient mouse models. The PPARα-null background did not rescue or aggravate the cardiac pathological development linked to cardiomyocyte-restricted PPARβ/δ deficiency. Moreover, PPARα-null did not alter the phenotypic development in adult mice with the short-term deletion of PPARβ/δ in their hearts, which showed mitochondrial abnormalities, depressed cardiac performance, and cardiac hypertrophy with attenuated expression of key factors in mitochondrial biogenesis and defense. The present study demonstrates that cardiomyocyte-restricted deletion of PPARβ/δ in PPARα-null mice causes impaired mitochondrial biogenesis and defense, but no further depression of fatty acid oxidation. Therefore, PPARβ/δ is essential for maintaining mitochondrial biogenesis and defense in cardiomyocytes independent of PPARα.
authors: Department of Nutrition Sciences, University of Alabama at Birmingham, 1675 University Boulevard, Birmingham, AL 35294-3360, USA.
authors: Jian
authors: J
authors: Liu
authors: Peiyong
authors: P
authors: Wang
authors: Lan
authors: L
authors: He
authors: Yuquan
authors: Y
authors: Li
authors: Jinwen
authors: J
authors: Luo
authors: Lihong
authors: L
authors: Cheng
authors: Qianhong
authors: Q
authors: Qin
authors: Lawrence A
authors: LA
authors: Brako
authors: Woo-Kuen
authors: WK
authors: Lo
authors: William
authors: W
authors: Lewis
authors: Qinglin
authors: Q
authors: Yang