دورية أكاديمية

11β-HSD1 Inhibitor Alleviates Non-Alcoholic Fatty Liver Disease by Activating the AMPK/SIRT1 Signaling Pathway

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