The peroxisome proliferator-activated receptors (PPARs) are involved in the regulation of most of the pathways linked to lipid metabolism. PPAR alpha and PPAR beta isotypes are known to regulate muscle fatty acid oxidation and a reciprocal compensation of their function has been proposed. Herein, we investigated muscle contractile and metabolic phenotypes in PPAR alpha-/-, PPAR beta(-/-), and double PPAR alpha-/-beta-/- mice. Heart and soleus muscle analyses show that the deletion of PPAR alpha induces a decrease of the HAD activity (P-oxidation) while soleus contractile phenotype remains unchanged. A PPARP deletion alone has no effect. However, these mild phenotypes are not due to a reciprocal compensation of PPARP and PPARot functions since double gene deletion PPAR alpha-PPAR beta mostly reproduces the null PPAR alpha-mediated reduced P-oxidation, in addition to a shift from fast to slow fibers. In conclusion, PPARP is not required for maintaining skeletal muscle metabolic activity and does not compensate the lack of PPARC alpha in PPARot null mice. (c) 2007 Elsevier Inc. All rights reserved.