Bedu Elodie, Wahli Walter, Desvergne Béatrice
Center for Integrative Genomics, University of Lausanne, CH-1015 Lausanne, Switzerland.
Expert Opin Ther Targets. 2005 Aug;9(4):861-73. doi: 10.1517/14728222.9.4.861.
The peroxisome proliferator-activated receptor (PPAR) family comprises three distinct isotypes: PPARalpha, PPARbeta/delta and PPARgamma. PPARs are nuclear hormone receptors that mediate the effects of fatty acids and their derivatives at the transcriptional level. Until recently, the characterisation of the important role of PPARalpha in fatty acid oxidation and of PPARgamma in lipid storage contrasted with the sparse information concerning PPARbeta/delta. However, evidence is now emerging for a role of PPARbeta/delta in tissue repair and energy homeostasis. Experiments with tissue-specific overexpression of PPARbeta/delta or treatment of mice with selective PPARbeta/delta agonists demonstrated that activation of PPARbeta/delta in vivo increases lipid catabolism in skeletal muscle, heart and adipose tissue and improves the serum lipid profile and insulin sensitivity in several animal models. PPARbeta/delta activation also prevents the development of obesity and improves cholesterol homeostasis in obesity-prone mouse models. These new insights into PPARbeta/delta functions suggest that targeting PPARbeta/delta may be helpful for treating disorders associated with the metabolic syndrome. Although these perspectives are promising, several independent and contradictory reports raise concerns about the safety of PPARbeta/delta ligands with respect to tumourigenic activity in the gut. Thus, it appears that further exploration of PPARbeta/delta functions is necessary to better define its potential as a therapeutic target.
过氧化物酶体增殖物激活受体（PPAR）家族由三种不同的亚型组成：PPARα、PPARβ/δ和PPARγ。PPAR是核激素受体，在转录水平介导脂肪酸及其衍生物的作用。直到最近，PPARα在脂肪酸氧化中的重要作用以及PPARγ在脂质储存中的作用已得到明确，这与关于PPARβ/δ的稀少信息形成对比。然而，现在有证据表明PPARβ/δ在组织修复和能量稳态中发挥作用。对PPARβ/δ进行组织特异性过表达或用选择性PPARβ/δ激动剂处理小鼠的实验表明，体内PPARβ/δ的激活会增加骨骼肌、心脏和脂肪组织中的脂质分解代谢，并改善几种动物模型中的血脂谱和胰岛素敏感性。PPARβ/δ激活还可预防肥胖的发生，并改善易肥胖小鼠模型中的胆固醇稳态。这些关于PPARβ/δ功能的新见解表明，靶向PPARβ/δ可能有助于治疗与代谢综合征相关的疾病。尽管这些观点很有前景，但一些独立且相互矛盾的报告引发了对PPARβ/δ配体在肠道肿瘤发生活性方面安全性的担忧。因此，似乎有必要进一步探索PPARβ/δ的功能，以更好地确定其作为治疗靶点的潜力。
