Fenofibrate Improves Insulin Resistance and Hepatic Steatosis and Regulates the Let-7/SERCA2b Axis in High-Fat Diet-Induced Non-Alcoholic Fatty Liver Disease Mice.
Fenofibrate Improves Insulin Resistance and Hepatic Steatosis and Regulates the Let-7/SERCA2b Axis in High-Fat Diet-Induced Non-Alcoholic Fatty Liver Disease Mice.
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非诺贝特改善高脂饮食诱导的非酒精性脂肪肝小鼠的胰岛素抵抗和肝脏脂肪变性并调节 Let-7/SERCA2b 轴
DOI：
10.3389/fphar.2021.770652
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发表时间：
2021
影响因子：
5.6
通讯作者：
Ma L
中科院分区：
文献类型：
--
作者：
Zhang D;Niu S;Ma Y;Chen H;Wen Y;Li M;Zhou B;Deng Y;Shi C;Pu G;Yang M;Wang X;Zou C;Chen Y;Ma L
非诺贝特被广泛用于临床治疗，以有效改善非酒精性脂肪性肝病（NAFLD）的发展；然而，其具体的分子作用机制在很大程度上仍不清楚。MicroRNAs （miRNAs）是NAFLD期间调节内质网（ER）应激的关键介质，miRNAs的失调已在NAFLD病理生理中得到证实。本研究旨在确定非诺贝特是否会影响NAFLD中miRNA的表达，并探讨非诺贝特在脂质代谢紊乱相关疾病中的具体作用机制。我们发现非诺贝特可以缓解内质网应激，并增加作为内质网应激调节因子的SERCA2b水平。此外，非诺贝特可以调节let-7 miRNA的水平；let-7被发现靶向SERCA2b的3 '非翻译区。目前的数据表明，非诺贝特对胰岛素抵抗的保护作用及其对肝脏过度脂质积累的抑制作用可能与改变let-7/SERCA2b轴和减轻内质网应激有关。
Fenofibrate is widely used in clinical therapy to effectively ameliorate the development of non-alcoholic fatty liver disease (NAFLD); however, its specific molecular mechanism of action remains largely unknown. MicroRNAs (miRNAs) are key mediators in regulating endoplasmic reticulum (ER) stress during NAFLD, and the deregulation of miRNAs has been demonstrated in NAFLD pathophysiology. The present study aimed to identify whether fenofibrate could influence miRNA expression in NAFLD and investigate the specific mechanism of action of fenofibrate in lipid metabolism disorder-associated diseases. We found that fenofibrate alleviated ER stress and increased the levels of SERCA2b, which serves as a regulator of ER stress. Additionally, the levels of let-7 miRNA were regulated by fenofibrate; let-7 was found to target the 3′ untranslated region of SERCA2b. The present data suggest that the protective effects of fenofibrate against insulin resistance and its suppressive activity against excessive hepatic lipid accumulation may be related to the alteration of the let-7/SERCA2b axis and alleviation of ER stress.
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影响因子：
5.9
作者：
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