Liang Xueli, Zhang Tianliang, Cheng Xinyi, Yuan Hang, Yang Ning, Yi Yanlei, Li Xiaozhou, Zhang Fengxiang, Sun Jinyue, Li Zhenfeng, Wang Xia
School of Public Health, Shandong Second Medical University, Weifang, China.
Experimental Center for Medical Research, Shandong Second Medical University, Weifang, China.
Front Nutr. 2024 Dec 20;11:1511682. doi: 10.3389/fnut.2024.1511682. eCollection 2024.
Non-alcoholic fatty liver disease (NAFLD) is a common chronic disease seriously threatening human health, with limited treatment means, however. Sesamin, a common lignan in sesame seed oil, exhibits anti-inflammatory, antioxidant, and anticancer properties. Our previous studies have shown an ameliorative effect of sesamin on lipid accumulation in human hepatocellular carcinoma (HePG2) induced by oleic acid, with its protective effects unclear in the case of 9-trans-C18:1 elaidic acid (9-trans-C18,1).
L02 cells, an important tool in scientific researches due to its high proliferation ability, preserved hepatocyte function, and specificity in response to exogenous factors, were incubated with 9-trans-C18:1 to establish an model of NAFLD in our study. The lipid accumulation in cells and the morphology of mitochondria and autolysosomes were observed by Oil Red O staining and transmission electron microscopy. The effects of sesamin on oxidative stress, apoptosis, mitochondrial function, autophagy as well as related protein levels in L02 cells were also investigated in the presence of 9-trans-C18:1.
The results showed that sesamin significantly accelerated the autophagy flux of L02 cells induced by 9-trans-C18:1 as well as elevated protein levels of transcription factor EB (TFEB) and its downstream target lysosome-associated membrane protein 1(LAMP1), along with up-regulated levels of TFEB and LAMP1 in the nucleus indicated by Immunofluorescence. In addition, PTEN-induced putative kinase 1 and Parkin mediated mitophagy was activated by sesamin. The direct inhibitor Eltrombopag and indirect inhibitor MHY1485 of TFEB reversed the protective effect of sesamin, suggesting the involvement of autophagy in the lipid-lowering process of sesamin.
This work suggests that sesamin regulates autophagy through TFEB to alleviate lipid accumulation in L02 cells induced by 9-trans-C18:1, providing a potential target for the prevention and treatment of NAFLD.
非酒精性脂肪性肝病（NAFLD）是一种严重威胁人类健康的常见慢性病，然而其治疗手段有限。芝麻素是芝麻油中常见的一种木脂素，具有抗炎、抗氧化和抗癌特性。我们之前的研究表明，芝麻素对油酸诱导的人肝癌细胞（HePG2）中的脂质积累有改善作用，但其对反式油酸（9-trans-C18:1）的保护作用尚不清楚。
L02细胞因其高增殖能力、保留的肝细胞功能以及对外源因素反应的特异性，是科学研究中的重要工具。在本研究中，将L02细胞与9-trans-C18:1孵育以建立NAFLD模型。通过油红O染色和透射电子显微镜观察细胞内的脂质积累以及线粒体和自噬体的形态。在存在9-trans-C18:1的情况下，还研究了芝麻素对L02细胞氧化应激、凋亡、线粒体功能、自噬以及相关蛋白水平的影响。
结果表明，芝麻素显著加速了9-trans-C18:1诱导的L02细胞的自噬通量，同时提高了转录因子EB（TFEB）及其下游靶标溶酶体相关膜蛋白1（LAMP1）的蛋白水平，免疫荧光显示细胞核中TFEB和LAMP1水平也上调。此外，芝麻素激活了PTEN诱导的假定激酶1和Parkin介导的线粒体自噬。TFEB的直接抑制剂艾曲泊帕和间接抑制剂MHY1485逆转了芝麻素的保护作用，表明自噬参与了芝麻素的降脂过程。
这项工作表明，芝麻素通过TFEB调节自噬，以减轻9-trans-C18:1诱导的L02细胞中的脂质积累，为NAFLD的预防和治疗提供了一个潜在靶点。
