Genistein enhances expression of genes involved in fatty acid catabolism through activation of PPARα
Genistein enhances expression of genes involved in fatty acid catabolism through activation of PPARα
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DOI：
10.1016/j.mce.2004.03.011
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发表时间：
2004-05-31
影响因子：
4.1
通讯作者：
Lee, MO
中科院分区：
文献类型：
--
作者：
Kim, S;Shin, HJ;Lee, MO
尽管越来越多的证据表明，膳食异黄酮对治疗高脂血症和心血管疾病有有益的作用，但其潜在的分子机制尚未得到广泛的表征。在本报告中，我们发现，通过实时逆转录酶聚合酶链反应和Western blotting分析，genstem，主要异黄酮之一，增加了HepG2细胞中参与脂质分解代谢的基因的表达，如肉碱棕榈酰基转移酶1，肝形式（CPT1L）。在强效雌激素受体抑制剂ICI182780存在的情况下，染料木素处理后CPT1L mrna水平的升高没有改变，提示染料木素的这种作用是雌激素受体无关的。由于这些参与脂肪酸分解代谢的基因被认为是过氧化物酶体增殖物激活受体α (pparα)的推定下游靶基因，我们研究了染料木素处理是否会调节pparα的表达。有趣的是，染料木素在mRNA和蛋白水平上诱导了pparα的表达。此外，通过报告基因分析，染料木黄酮激活了pparα的转录活性，表明染料木黄酮可能是pparα的潜在配体。综上所述，本研究提供了染料木素作为ppar - α激活剂在脂肪酸分解代谢中的调节作用以及染料木素作为降脂剂的潜在用途。2004爱思唯尔爱尔兰有限公司版权所有。
Although evidences are emerging that dietary isoflavones have beneficial effects in treatment of hyperlipidemia and cardiovascular diseases, the underlying molecular mechanism has not yet been extensively characterized. In this report, we showed that genistem, one of the major isoflavones, increased expression of genes involved in lipid catabolism such as carnitine palmitoyltransferase 1, liver form (CPT1L) in HepG2 cells, when assayed by real-time reverse-transcriptase polymerase chain reactions as well as Western blotting analysis. The increase in mRNA-level of CPT1L after genistem treatment was not changed in the presence of ICI182780, a potent inhibitor of estrogen receptor, suggesting that this effect of genistein was estrogen receptor-independent. Since these genes involved in fatty acid catabolism are considered putative downstream target genes of peroxisome proliferators-activated receptor alpha (PPARalpha), we examined whether expression of PPARalpha was modulated by genistein treatment. Interestingly, genistein induced expression of PPARalpha at both mRNA- and protein-level. Further, genistein activated transcriptional activity of PPARalpha, when determined by reporter gene analysis, suggesting genistein as a potential ligand for PPARalpha. Taken together, this study provides a picture of the regulatory action of genistein, as an activator of PPARalpha in fatty acid catabolism and potential use of genistein as lipid-lowering agent. (C) 2004 Elsevier Ireland Ltd. All rights reserved.