Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju 220-701, Republic of Korea.
The East Coast Research Institute of Life Science, Gangneung-Wonju National University, Gangneung, Republic of Korea.
Metabolism. 2020 Feb;103:154015. doi: 10.1016/j.metabol.2019.154015. Epub 2019 Nov 20.
Nonalcoholic fatty liver disease (NAFLD) occurs when excess fat storage in the liver and it is strongly linked with metabolic syndrome including obesity, insulin resistance, dyslipidemia and hypertension. Curcumin5-8 (CUR5-8) is a synthetic derivative of naturally active curcumin (CUR) that has anti-oxidative and anti-inflammatory properties. In the present study, we investigated the effects of CUR5-8, a novel CUR analog, on hepatic steatosis in mice with high-fat diet (HFD)-induced obesity.
Based on their diets for 13 weeks, the mice were categorized into the following six groups: regular diet (RD, n = 10), RD with CUR (RD + CUR, 100 mg/kg/day, n = 10), RD with CUR5-8 (RD + CUR5-8, 100 mg/kg/day, n = 10), high-fat diet-induced obese mice (HFD, n = 10), HFD with CUR (HFD + CUR, 100 mg/kg/day, n = 10), and HFD with CUR5-8 (HFD + CUR5-8, 100 mg/kg/day, n = 10) for 13 weeks. Hematoxylin and eosin (H&E) staining of the sections revealed hepatic steatosis.
CUR5-8 administration prevented increase in body and liver weights in mice with HFD-induced obesity. Compared to the HFD group, insulin resistance was significantly improved in the HFD + CUR5-8 group. Serum alanine aminotransferase level, which is an indicator of liver damage, was also decreased after CUR5-8 administration. H&E staining revealed that CUR5-8 treatment decreased hepatic steatosis in mice with HFD-induced obesity. Interestingly, CUR5-8, and not CUR, decreased the elevated liver triglyceride level induced by the HFD.
These findings suggest that CUR5-8 ameliorates insulin resistance and hepatic steatosis in mice with HFD-induced obesity.
当肝脏内脂肪储存过多时，就会发生非酒精性脂肪性肝病（NAFLD），它与包括肥胖、胰岛素抵抗、血脂异常和高血压在内的代谢综合征密切相关。姜黄素 5-8（CUR5-8）是天然姜黄素（CUR）的一种合成衍生物，具有抗氧化和抗炎特性。在本研究中，我们研究了新型 CUR 类似物 CUR5-8 对高脂肪饮食（HFD）诱导肥胖小鼠肝脂肪变性的影响。
根据其 13 周的饮食，将小鼠分为以下六组：普通饮食（RD，n=10）、RD 加 CUR（RD+CUR，100mg/kg/天，n=10）、RD 加 CUR5-8（RD+CUR5-8，100mg/kg/天，n=10）、高脂肪饮食诱导肥胖小鼠（HFD，n=10）、HFD 加 CUR（HFD+CUR，100mg/kg/天，n=10）和 HFD 加 CUR5-8（HFD+CUR5-8，100mg/kg/天，n=10）共 13 周。肝组织切片的苏木精和伊红（H&E）染色显示肝脂肪变性。
CUR5-8 给药可预防 HFD 诱导肥胖小鼠体重和肝脏重量的增加。与 HFD 组相比，HFD+CUR5-8 组胰岛素抵抗显著改善。血清丙氨酸氨基转移酶水平（一种肝损伤标志物）在 CUR5-8 给药后也降低。H&E 染色显示，CUR5-8 治疗可减少 HFD 诱导肥胖小鼠的肝脂肪变性。有趣的是，CUR5-8 而非 CUR 降低了 HFD 诱导的肝甘油三酯水平升高。
这些发现表明，CUR5-8 可改善 HFD 诱导肥胖小鼠的胰岛素抵抗和肝脂肪变性。
