Functional Cellular Networks Laboratory, Department of Medicine, College of Medicine, Graduate School and Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon 21999, Korea.
Department of Anatomy & Cell Biology, Gachon University College of Medicine, Incheon 21936, Korea.
Mar Drugs. 2021 May 30;19(6):318. doi: 10.3390/md19060318.
Nonalcoholic fatty liver disease (NAFLD), which promotes serious health problems, is related to the increase in the nucleotide-binding oligomerization domain-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome and pyroptosis by a high-fat diet (HFD). Whether dieckol (DK), a component of extracts (ECE), attenuated NAFLD in an HFD-induced NAFLD animal model was evaluated. The expression of high mobility group box 1/Toll-like receptor 4/nuclear factor-κB, which initiated the NLRP3 inflammasome, was increased in the liver of HFD-fed animals and significantly decreased with ECE or DK administration. The expression of NLRP3/ASC/caspase-1, which are components of the NLRP3 inflammasome, and the number of pyroptotic cells were increased by HFD and decreased with ECE or DK administration. The accumulation of triglycerides and free fatty acids in the liver was increased by HFD and decreased with ECE or DK administration. The histological NAFLD score was increased by HFD and decreased with ECE or DK administration. The expression of lipogenic genes (FASN, SREBP-2, PPARγ, and FABP4) increased and that of lipolytic genes (PPARα, CPT1A, ATGL, and HSL) was decreased by HFD and attenuated with ECE or DK administration. In conclusion, ECE or DK attenuated NAFLD by decreasing the NLRP3 inflammasome and pyroptosis.
非酒精性脂肪性肝病（NAFLD）可导致严重的健康问题，其与核苷酸结合寡聚化结构域样受体家族、含吡咯并嘧啶结构域蛋白 3（NLRP3）炎性小体和细胞焦亡的增加有关，而这些改变是由高脂肪饮食（HFD）引起的。本研究旨在评估 提取物（ECE）的一种成分二酮（DK）是否能减轻 HFD 诱导的 NAFLD 动物模型中的 NAFLD。结果发现，ECE 或 DK 可降低高脂肪饮食喂养动物肝脏中高迁移率族蛋白 B1/Toll 样受体 4/核因子-κB 的表达，该蛋白可启动 NLRP3 炎性小体。ECE 或 DK 还可降低 NLRP3/ASC/caspase-1 的表达以及细胞焦亡的数量，而 NLRP3/ASC/caspase-1 是 NLRP3 炎性小体的组成部分。ECE 或 DK 还可降低甘油三酯和游离脂肪酸在肝脏中的积累。ECE 或 DK 还可降低组织学 NAFLD 评分。ECE 或 DK 还可降低脂肪生成基因（FASN、SREBP-2、PPARγ 和 FABP4）的表达，并增加脂肪分解基因（PPARα、CPT1A、ATGL 和 HSL）的表达，而这些改变是由 HFD 引起的。综上所述，ECE 或 DK 通过降低 NLRP3 炎性小体和细胞焦亡来减轻 NAFLD。
