The Jackson Laboratory, ME, USA.
PPAR Res. 2007;2007:12781. doi: 10.1155/2007/12781.
The interest in genetic manipulations of PPARs is as old as their discovery as receptors of ligands with beneficial clinical activities. Considering the effects of PPAR ligands on critical aspects of systemic physiology, including obesity, lipid metabolism, insulin resistance, and diabetes, gene knockout (KO) in mice is the ideal platform for both hypothesis testing and discovery of new PPAR functions in vivo. With the fervent pursuit of the magic bullet to eradicate the obesity epidemic, special emphasis has been placed on the impacts of PPARs on obesity and its associated diseases. As detailed in this review, understanding how PPARs regulate gene expression and basic metabolic pathways is a necessary intermediate en route to deciphering their effects on obesity. Over a decade and dozens of genetic modifications of PPARs into this effort, valuable lessons have been learned, but we are left with more questions to be answered. These lessons and future prospects are the subject of this review.
人们对过氧化物酶体增殖物激活受体 (PPARs) 的基因操作的兴趣可以追溯到它们被发现为具有临床益处的配体的受体之时。鉴于 PPAR 配体对系统生理学的关键方面（包括肥胖、脂质代谢、胰岛素抵抗和糖尿病）的影响，小鼠的基因敲除 (KO) 是在体内进行假设检验和发现新的 PPAR 功能的理想平台。随着对消除肥胖流行的“魔弹”的热切追求，人们特别关注 PPARs 对肥胖及其相关疾病的影响。正如本综述中详细介绍的那样，了解 PPARs 如何调节基因表达和基本代谢途径是破译它们对肥胖影响的必要中间步骤。在这项努力中进行了十多年和数十种 PPAR 的基因修饰，已经吸取了宝贵的经验教训，但我们仍有更多问题需要解答。这些经验教训和未来展望是本综述的主题。
