Luquet Serge, Lopez-Soriano Joaquin, Holst Dorte, Fredenrich Alexandre, Melki Judith, Rassoulzadegan Minoo, Grimaldi Paul A
Inserm U470, Centre de Biochimie, Parc Valrose, Université de Nice-Sophia Antipolis, 06108 Nice cedex 2, France.
FASEB J. 2003 Dec;17(15):2299-301. doi: 10.1096/fj.03-0269fje. Epub 2003 Oct 2.
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.
过氧化物酶体增殖物激活受体（PPARs）是在发育和代谢中发挥多种功能的核受体。PPARδ的生理功能仍不清楚。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过表达由于增生和/或向更多氧化型纤维的转变而导致纤维组成发生深刻变化，结果导致氧化代谢相关的酶活性和基因均增加。肌肉中的这些变化伴随着体脂量的减少，这主要是由于脂肪细胞大小的大幅减小。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。总体而言，这些结果表明PPARδ在肌肉发育和对环境变化（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可能有利于预防代谢紊乱（如肥胖或2型糖尿病）的观点。
