Esculetin prevents non-alcoholic fatty liver in diabetic mice fed high-fat diet
Esculetin prevents non-alcoholic fatty liver in diabetic mice fed high-fat diet
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DOI：
10.1016/j.cbi.2016.10.013
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发表时间：
2016-12-25
影响因子：
5.1
通讯作者：
Lee, Mi-Kyung
中科院分区：
文献类型：
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作者：
Choi, Ra-Yeong;Ham, Ju Ri;Lee, Mi-Kyung
本研究探讨了esculetin（6,7-二羟基香豆素）对高脂饮食（HFD）糖尿病小鼠非酒精性脂肪肝的影响及其机制。采用链脲佐菌素诱导糖尿病小鼠模型，分别饲喂加或不加埃斯维素的高脂饲料11周。非糖尿病小鼠给予正常饮食。糖尿病引起肝脏肥厚、脂质积聚和微滴；然而，esculetin逆转了这些变化。Esculetin处理可显著下调脂质合成基因Fasn、Dgat2和Plpp2以及炎症基因Tlr4、Myd88、Nfkb、Tnf α和Il6的表达。此外，与糖尿病组相比，esculetin组肝脏脂质合成酶（脂肪酸合成酶和磷脂磷酸水解酶）和糖异生酶（葡萄糖-6-磷酸酶）活性降低。此外，与糖尿病组相比，esculetin显著降低了血液HbA（1c）、血清细胞因子（tnf - α和IL-6）和趋化因子（MCP-1）水平，而血清和胰腺中的胰岛素含量没有改变。糖尿病组肝脏SOD活性低于正常组，脂质过氧化水平高于正常组；然而，esculletin减弱了这些差异。总的来说，这些结果表明，补充esculetin可以通过调节脂质、葡萄糖和炎症来防止糖尿病患者非酒精性脂肪肝的发展。2016爱思唯尔爱尔兰有限公司版权所有。
This study investigated the effects and mechanism of esculetin (6,7-dihydroxycoumarin) on non-alcoholic fatty liver in diabetic mice fed high-fat diet (HFD). The diabetic mice model was induced by injection of streptozotocin, after which they were fed HFD diet with or without esculetin for 11 weeks. Non-diabetic mice were provided a normal diet. Diabetes induced hepatic hypertrophy, lipid accumulation and droplets; however, esculetin reversed these changes. Esculetin treatment in diabetic mice fed HFD significantly down-regulated expression of lipid synthesis genes (Fasn, Dgat2 and Plpp2) and inflammation genes (Tlr4, Myd88, Nfkb, Tnf alpha and Il6). Moreover, the activities of hepatic lipid synthesis enzymes (fatty acid synthase and phosphatidate phosphohydrolase) and gluconeogenesis enzyme (glucose-6-phosphatase) in the esculetin group were decreased compared with the diabetic group. In addition, esculetin significantly reduced blood HbA(1c), serum cytokines (TNF-alpha and IL-6) and chemokine (MCP-1) levels compared with the diabetic group without changing the insulin content in serum and the pancreas. Hepatic SOD activity was lower and lipid peroxidation level was higher in the diabetic group than in the normal group; however, esculetin attenuates these differences. Overall, these results demonstrated that esculetin supplementation could protect against development of non-alcoholic fatty liver in diabetes via regulation of lipids, glucose and inflammation. (C) 2016 Elsevier Ireland Ltd. All rights reserved.