Inhibition of liver X receptor-α-dependent hepatic steatosis by isoliquiritigenin, a licorice antioxidant flavonoid, as mediated by JNK1 inhibition
Inhibition of liver X receptor-α-dependent hepatic steatosis by isoliquiritigenin, a licorice antioxidant flavonoid, as mediated by JNK1 inhibition
复制标题
DOI：
10.1016/j.freeradbiomed.2010.09.001
复制
发表时间：
2010-12-01
影响因子：
7.4
通讯作者：
Kim, Sang Geon
中科院分区：
文献类型：
--
作者：
Kim, Young Mi;Kim, Tae Hyun;Kim, Sang Geon
异甘草素 (ILQ) 是一种从甘草中提取的黄酮类化合物，具有抗氧化作用。本研究调查了 ILQ 抑制肝脏 X 受体 α (LXR α) 介导的肝细胞脂肪生成和脂肪变性的潜力及其潜在分子基础。ILQ 治疗拮抗 LXR α 激动剂 (10901317) 激活甾醇调节元件结合蛋白 1c 的能力(SREBP-1c) 从而抑制脂肪酸合酶乙酰 CoA 羧化酶 ATP 结合盒转运蛋白 A1 和硬脂酰 CoA 去饱和酶 1 的转录 ILQ 治疗抑制由棕榈酸酯或 TNF α JNK1 而非 JNK2 引起的 JNK1 磷酸化激活 增加丝氨酸残基处的 LXR α 磷酸化，促进 LXR α 激活 ILQ 抑制 JNK1 下游的能力ASK1-MKK7 导致抑制 T0901317 诱导的 LXR α 和 SREBP 1c 激活 在喂食高脂饮食的小鼠中，ILQ 治疗可抑制肝脏脂肪变性，表现为脂肪积累减少和脂肪生成基因的抑制 血液生化和组织病理学结果证实 ILQ 可以减轻高脂饮食诱导的肝损伤 此外，ILQ 抑制氧化应激（表现为 throbai bitulc 的减少）酸反应物质形成 iNOS 和 COX2 诱导以及硝基酪氨酸化 我们的结果表明，ILQ 能够通过 JNK1 抑制来抑制 LXR α 依赖性肝脂肪变性，并保护肝细胞免受脂肪堆积造成的氧化损伤 (C) 2010 Elsevier Inc 保留所有权利
Isoliguritigenin (ILQ) a flavonoid obtained from Glycyrrhizae species has an antioxidant effect This study investigated the potential of ILQ for inhibiting liver X receptor alpha (LXR alpha) mediated lipogenesis and steatosis in hepatocytes and its underlying molecular basis Treatment with ILQ antagonized the ability of an LXR alpha agonist (10901317) to activate sterol regulatory element binding protein 1c (SREBP-1c) thereby repressing transcription of fatty acid synthase acetyl CoA carboxylase ATP-binding cassette transporter A1 and stearoyl CoA desaturase 1 ILQ treatment inhibited activating phosphorylation of JNK1 elicited by palmitate or TNF alpha JNK1 but not JNK2 increased LXR alpha phosphorylation at serine residues promoting LXR alpha activation The ability of ILQ to inhibit JNK1 downstream of ASK1-MKK7 led to the repression of T0901317-inducible LXR alpha and SREBP 1c activation In mice fed a high-fat diet ILQ treatment inhibited hepatic steatosis as shown by a decrease in fat accumulation and repression of lipogenic genes The results of blood biochemistry and histopathology confirmed attenuation of high fat diet induced liver injury by ILQ Moreover ILQ inhibited oxidative stress as indicated by decreases in throbai bituilc acid-reactive substance formation iNOS and COX2 induction and nitrotyrosinylation Our results demonstrate that ILQ has the ability to repress LXR alpha dependent hepatic steatosis through JNK1 inhibition and protect hepatocytes from oxidative injury inflicted by fat accumulation (C) 2010 Elsevier Inc All rights reserved