التفاصيل البيبلوغرافية
العنوان: |
11β-HSD1 Inhibitor Alleviates Non-Alcoholic Fatty Liver Disease by Activating the AMPK/SIRT1 Signaling Pathway |
المؤلفون: |
Ying Chen, Jiali Li, Meng Zhang, Wei Yang, Wenqi Qin, Qinzhou Zheng, Yanhui Chu, Yan Wu, Dan Wu, Xiaohuan Yuan |
المصدر: |
Nutrients; Volume 14; Issue 11; Pages: 2358 |
بيانات النشر: |
Multidisciplinary Digital Publishing Institute |
سنة النشر: |
2022 |
المجموعة: |
MDPI Open Access Publishing |
مصطلحات موضوعية: |
11-beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1), curcumin, non-alcoholic fatty liver disease (NAFLD), lipid metabolism, anti-inflammatory |
جغرافية الموضوع: |
agris |
الوصف: |
We investigated the effect of an 11β-HSD1 inhibitor (H8) on hepatic steatosis and its mechanism of action. Although H8, a curcumin derivative, has been shown to alleviate insulin resistance, its effect on non-alcoholic fatty liver disease (NAFLD) remains unknown. Rats were fed a high-fat diet (HFD) for 8 weeks, intraperitoneally injected with streptozotocin (STZ) to induce NAFLD, and, then, treated with H8 (3 or 6 mg/kg/day) or curcumin (6 mg/kg/day) for 4 weeks, to evaluate the effects of H8 on NAFLD. H8 significantly alleviated HFD+STZ-induced lipid accumulation, fibrosis, and inflammation as well as improved liver function. Moreover, 11β-HSD1 overexpression was established by transfecting animals and HepG2 cells with lentivirus, carrying the 11β-HSD1 gene, to confirm that H8 improved NAFLD, by reducing 11β-HSD1. An AMP-activated protein kinase (AMPK) inhibitor (Compound C, 10 μM for 2 h) was used to confirm that H8 increased AMPK, by inhibiting 11β-HSD1, thereby restoring lipid metabolic homeostasis. A silencing-related enzyme 1 (SIRT1) inhibitor (EX572, 10 μM for 4 h) and a SIRT1 activator (SRT1720, 1 μM for 4 h) were used to confirm that H8 exerted anti-inflammatory effects, by elevating SIRT1 expression. Our findings demonstrate that H8 alleviates hepatic steatosis, by inhibiting 11β-HSD1, which activates the AMPK/SIRT1 signaling pathway. |
نوع الوثيقة: |
text |
وصف الملف: |
application/pdf |
اللغة: |
English |
العلاقة: |
Nutrition and Diabetes; https://dx.doi.org/10.3390/nu14112358Test |
DOI: |
10.3390/nu14112358 |
الإتاحة: |
https://doi.org/10.3390/nu14112358Test |
حقوق: |
https://creativecommons.org/licenses/by/4.0Test/ |
رقم الانضمام: |
edsbas.1611719F |
قاعدة البيانات: |
BASE |