Lehrke Michael, Lazar Mitchell A
Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, and The Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Cell. 2005 Dec 16;123(6):993-9. doi: 10.1016/j.cell.2005.11.026.
In an era marked by the increasing prevalence of obesity, diabetes, and cardiovascular disease, the nuclear receptor peroxisome proliferator-activated receptor gamma (PPARgamma) has emerged as a transcriptional regulator of metabolism whose activity can be modulated by direct binding of small molecules. As the master regulator of fat-cell formation, PPARgamma is required for the accumulation of adipose tissue and hence contributes to obesity. Yet PPARgamma ligands are clinically effective antidiabetic drugs, although side effects limit their utility. Can PPARgamma be targeted with greater benefit and with less risk to patients? The answer depends upon the basic biology of PPARgamma, and the possibility of selectively modulating the activity of this nuclear receptor in a tissue- and target-gene-specific manner.
在一个肥胖、糖尿病和心血管疾病患病率不断上升的时代，核受体过氧化物酶体增殖物激活受体γ（PPARγ）已成为一种代谢转录调节因子，其活性可通过小分子的直接结合来调节。作为脂肪细胞形成的主要调节因子，PPARγ是脂肪组织积累所必需的，因此导致肥胖。然而，PPARγ配体是临床上有效的抗糖尿病药物，尽管副作用限制了它们的应用。能否以更大的益处和更低的风险靶向PPARγ？答案取决于PPARγ的基础生物学，以及以组织和靶基因特异性方式选择性调节这种核受体活性的可能性。
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