Bedu E, Desplanches D, Pequignot J, Bordier B, Desvergne B
Center of Integrative Genomics, University of Lausanne, CH-1015 Lausanne, Switzerland.
Biochem Biophys Res Commun. 2007 Jun 15;357(4):877-81. doi: 10.1016/j.bbrc.2007.04.003. Epub 2007 Apr 9.
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.
过氧化物酶体增殖物激活受体（PPARs）参与调控大多数与脂质代谢相关的途径。已知PPARα和PPARβ亚型可调节肌肉脂肪酸氧化，并且有人提出它们的功能存在相互补偿作用。在此，我们研究了PPARα基因敲除小鼠、PPARβ基因敲除小鼠以及PPARα和PPARβ双基因敲除小鼠的肌肉收缩和代谢表型。心脏和比目鱼肌分析表明，PPARα基因缺失会导致HAD活性（β氧化）降低，而比目鱼肌的收缩表型保持不变。单独敲除PPARβ没有影响。然而，这些轻微的表型并非由于PPARβ和PPARα功能的相互补偿，因为双基因敲除PPARα - PPARβ除了导致纤维类型从快肌纤维向慢肌纤维转变外，大多重现了PPARα基因敲除介导的β氧化减少。总之，维持骨骼肌代谢活性不需要PPARβ，并且在PPARα基因敲除小鼠中PPARβ不能补偿PPARα的缺失。
