Double gene deletion reveals the lack of cooperation between PPARα and PPARβ in skeletal muscle
Double gene deletion reveals the lack of cooperation between PPARα and PPARβ in skeletal muscle
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DOI：
10.1016/j.bbrc.2007.04.003
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发表时间：
2007-06-15
影响因子：
3.1
通讯作者：
Desvergne, B.
中科院分区：
文献类型：
--
作者：
Bedu, E.;Desplanches, D.;Desvergne, B.
过氧化物酶体增殖物激活受体 (PPAR) 参与调节大多数与脂质代谢相关的途径。已知 PPAR α 和 PPAR β 同种型可调节肌肉脂肪酸氧化，并且已提出其功能的相互补偿。在此，我们研究了 PPAR α-/-、PPAR β(-/-) 和双 PPAR α-/- β-/- 小鼠的肌肉收缩和代谢表型。心脏和比目鱼肌分析表明，PPAR α 的缺失会导致 HAD 活性（P 氧化）降低，而比目鱼肌收缩表型保持不变。单独删除 PPARP 没有效果。然而，这些温和的表型并不是由于 PPARP 和 PPARot 功能的相互补偿，因为除了从快纤维向慢纤维的转变之外，双基因缺失 PPAR α-PPAR β 主要再现无效的 PPAR α 介导的 P-氧化减少。总之，PPARP 不是维持骨骼肌代谢活性所必需的，并且不能补偿 PPARot 缺失小鼠中 PPARC α 的缺乏。 (c) 2007 Elsevier Inc. 保留所有权利。
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.