title: Double gene deletion reveals the lack of cooperation between PPARalpha and PPARbeta in skeletal muscle.
abstract: The peroxisome proliferator-activated receptors (PPARs) are involved in the regulation of most of the pathways linked to lipid metabolism. PPARalpha and PPARbeta 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 PPARalpha-/-, PPARbeta-/-, and double PPARalpha-/- beta-/- mice. Heart and soleus muscle analyses show that the deletion of PPARalpha induces a decrease of the HAD activity (beta-oxidation) while soleus contractile phenotype remains unchanged. A PPARbeta deletion alone has no effect. However, these mild phenotypes are not due to a reciprocal compensation of PPARbeta and PPARalpha functions since double gene deletion PPARalpha-PPARbeta mostly reproduces the null PPARalpha-mediated reduced beta-oxidation, in addition to a shift from fast to slow fibers. In conclusion, PPARbeta is not required for maintaining skeletal muscle metabolic activity and does not compensate the lack of PPARalpha in PPARalpha null mice.
authors.affiliation: Center of Integrative Genomics, University of Lausanne, CH-1015 Lausanne, Switzerland.
authors.forename: E
authors.initials: E
authors.lastname: Bedu
authors.forename: D
authors.initials: D
authors.lastname: Desplanches
authors.forename: J
authors.initials: J
authors.lastname: Pequignot
authors.forename: B
authors.initials: B
authors.lastname: Bordier
authors.forename: B
authors.initials: B
authors.lastname: Desvergne
mesh_terms: D000818:Animals; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009097:Multienzyme Complexes / Q000378:metabolism*; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism*; D048068:PPAR-beta / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D014018:Tissue Distribution
chemical_list: D009097:Multienzyme Complexes; D047493:PPAR alpha; D048068:PPAR-beta