The Role of PPAR-δ in Metabolism, Inflammation, and Cancer: Many Characters of a Critical Transcription Factor.
The Role of PPAR-δ in Metabolism, Inflammation, and Cancer: Many Characters of a Critical Transcription Factor.
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DOI：
10.3390/ijms19113339
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发表时间：
2018-10-26
影响因子：
5.6
通讯作者：
Shureiqi I
中科院分区：
文献类型：
--
作者：
Liu Y;Colby JK;Zuo X;Jaoude J;Wei D;Shureiqi I
过氧化物酶体增殖物激活受体-δ（Peroxisome proliferator-activated receptor-δ，PPAR-δ）是核受体超家族中的三个成员之一，是配体激活的转录因子。PPAR-δ调节重要的细胞代谢功能，有助于维持能量平衡。PPAR-δ在调节脂肪酸摄取、转运和β-氧化以及胰岛素分泌和敏感性方面尤其重要。正常细胞中这些有益的PPAR-δ功能被认为可以防止代谢综合征相关疾病，如肥胖症、血脂异常、胰岛素抵抗/2型糖尿病、脂肪肝和动脉粥样硬化。鉴于这些疾病造成的高临床负担，开发了高选择性的合成的PPAR-δ活化配体作为潜在的预防/治疗剂。其中一些化合物在针对代谢综合征相关疾病的临床试验中显示出一定的疗效。然而，PPAR-δ激动剂的临床开发被停止，因为各种证据表明癌细胞上调PPAR-δ表达/活性作为对抗营养剥夺和能量应激的防御机制，改善其存活率并促进癌症进展。这篇综述讨论了PPAR-δ在健康和疾病中的复杂关系，并强调了我们目前对PPAR-δ在代谢、炎症和癌症中发挥的不同作用的认识。
Peroxisome proliferator-activated receptor-delta (PPAR-δ), one of three members of the PPAR group in the nuclear receptor superfamily, is a ligand-activated transcription factor. PPAR-δ regulates important cellular metabolic functions that contribute to maintaining energy balance. PPAR-δ is especially important in regulating fatty acid uptake, transport, and β-oxidation as well as insulin secretion and sensitivity. These salutary PPAR-δ functions in normal cells are thought to protect against metabolic-syndrome-related diseases, such as obesity, dyslipidemia, insulin resistance/type 2 diabetes, hepatosteatosis, and atherosclerosis. Given the high clinical burden these diseases pose, highly selective synthetic activating ligands of PPAR-δ were developed as potential preventive/therapeutic agents. Some of these compounds showed some efficacy in clinical trials focused on metabolic-syndrome-related conditions. However, the clinical development of PPAR-δ agonists was halted because various lines of evidence demonstrated that cancer cells upregulated PPAR-δ expression/activity as a defense mechanism against nutritional deprivation and energy stresses, improving their survival and promoting cancer progression. This review discusses the complex relationship between PPAR-δ in health and disease and highlights our current knowledge regarding the different roles that PPAR-δ plays in metabolism, inflammation, and cancer.
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DOI：
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发表时间：
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影响因子：
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作者：
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通讯作者：
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