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

It is well documented that ppar 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 ppar knockout shows a benign cardiac phenotype. it is unknown whether a ppar-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 ppar-null background showed a comparably reduced cardiac expression of lipid metabolism to those of single ppar-deficient mouse models. the ppar-null background did not rescue or aggravate the cardiac pathological development linked to cardiomyocyte- restricted pparβ/δ deficiency. moreover,ppar-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 ppar-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 ppar. © 2011 jian liu et al.