Peroxisome proliferator-activated receptor δ controls muscle development and oxydative capability
Peroxisome proliferator-activated receptor δ controls muscle development and oxydative capability
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DOI：
10.1096/fj.03-0269fje
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发表时间：
2003-10-01
期刊：
影响因子：
4.8
通讯作者：
Grimaldi, PA
中科院分区：
文献类型：
--
作者：
Luquet, S;Lopez-Soriano, J;Grimaldi, PA
过氧化物酶体增殖物激活受体（PPARs）是核受体，在发育和代谢中具有多种功能。PPARδ的生理功能仍不明确。通过使用CRE - Lox重组方法，我们构建了一个肌肉特异性PPARδ过表达的动物模型，以研究PPARδ在该组织中的作用。肌肉特异性PPARδ过表达导致由于增生和/或向更具氧化性的纤维转变而引起的纤维组成发生显著变化，结果导致氧化代谢相关的酶活性和基因增加。肌肉中的这些变化伴随着体脂肪量的减少，这主要是由于脂肪细胞大小大幅减小。此外，我们证明耐力运动促进野生型动物肌肉中PPARδ蛋白的积累。总之，这些结果表明PPARδ在肌肉发育以及对环境变化（如训练运动）的适应性反应中起重要作用。它们有力地支持了激活PPARδ可能对预防代谢紊乱（如肥胖或2型糖尿病）有益的观点。
Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors exerting several functions in development and metabolism. The physiological functions of PPARdelta remain elusive. By using a CRE-Lox recombination approach, we generated an animal model for muscle-specific PPARdelta overexpression to investigate the role of PPARdelta in this tissue. Muscle-specific PPARdelta overexpression results in a profound change in fiber composition due to hyperplasia and/or shift to more oxidative fiber and, as a consequence, leads to the increase of both enzymatic activities and genes implicated in oxidative metabolism. These changes in muscle are accompanied by a reduction of body fat mass, mainly due to a large reduction of adipose cell size. Furthermore, we demonstrate that endurance exercise promotes an accumulation of PPARdelta protein in muscle of wild-type animals. Collectively, these results suggest that PPARdelta plays an important role in muscle development and adaptive response to environmental changes, such as training exercise. They strongly support the idea that activation of PPARdelta could be beneficial in prevention of metabolic disorders, such as obesity or type 2 diabetes.