LB100 ameliorates nonalcoholic fatty liver disease via the AMPK/Sirt1 pathway

作者：Xueyang Chen, Changzhou Cai, Mengli Yu, Zemin Feng, Yu-Wei Zhang, Peihao Liu, Hang Zeng, Chaohui Yu · 发表于：World Journal of Gastroenterology · 年份：2019 · DOI：10.3748/wjg.v25.i45.6607 · 被引用次数：61 · 研究领域：Sirtuins and Resveratrol in Medicine、Adipose Tissue and Metabolism、Liver Disease Diagnosis and Treatment

BACKGROUND: It is well known that nonalcoholic fatty liver disease (NAFLD) is associated with insulin resistance (IR). LB100, a serine/threonine protein phosphatase 2A (PP2A) inhibitor, is closely related to IR. However, there is little data regarding its direct influence on NAFLD. AIM: To elucidate the effect and underlying mechanism of LB100 in NAFLD. METHODS: After 10 wk of high fat diet (HFD) feeding, male C57BL/6 mice were injected intraperitoneally with vehicle or LB100 for an additional 6 wk (three times a week). The L02 cell line was treated with LB100 and free fatty acids (FFAs) for 24 h. Hematoxylin and eosin and oil red O staining were performed for histological examination. Western blot analysis was used to detect the protein expression of Sirtuin 1 (Sirt1), total and phosphorylated AMP-activated protein kinase α (AMPKα), and the proteins involved in lipogenesis and fatty acid oxidation. The mRNA levels were determined by qPCR. Pharmacological inhibition of AMPK was performed to further examine the exact mechanism of LB100 in NAFLD. RESULTS: , LB100 alleviated FFA-induced lipid accumulation in L02 cells through the AMPK/Sirt1 signaling pathway. Further studies showed that the curative effect of LB100 on lipid accumulation was abolished by inhibiting AMPKα in L02 cells. CONCLUSION: the AMPK/Sirt1 pathway. LB100 may be a potential therapeutic agent for NAFLD.