Department of Nutrition and Food Hygiene, School of Public Health, Shanxi Medical University, Taiyuan, Shanxi, PR China.
Department of Nutrition and Food Hygiene, School of Public Health, Shanxi Medical University, Taiyuan, Shanxi, PR China.
J Nutr Biochem. 2022 Sep;107:109072. doi: 10.1016/j.jnutbio.2022.109072. Epub 2022 Jun 3.
Apoptosis is a feature of progressions steatosis to nonalcoholic steatohepatitis (NASH) and can be explained by endoplasmic reticulum stress (ERS). The present study aimed to investigate the protective effects of plant sterol ester of α-linolenic acid (PS-ALA) on ERS-triggered apoptosis in high fat diet-fed mice and oleic acid-induced hepatocytes, and further explore the underlying mechanisms. Our results showed that PS-ALA improved Non-alcoholic fatty liver disease (NAFLD) in both in vivo and in vitro models. Moreover, PS-ALA treatment can attenuate ERS and associated apoptosis via inhibiting IRE1α/TRAF2/JNK signal pathway. Furthermore, we found that the protective effect of PS-ALA on ERS-triggered apoptosis was mediated by activation of AMP-activated protein kinase (AMPK) as pretreatment with Compound C, an AMPK inhibitor, abolished the anti-apoptotic effect of PS-ALA. Taken together, our results illustrate that PS-ALA attenuating ERS-mediated apoptosis via activating AMPK, which provided new insights into the protective effect of PS-ALA in NAFLD.
细胞凋亡是脂肪性肝炎（NASH）发生进展的一个特征，这可以通过内质网应激（ERS）来解释。本研究旨在探讨α-亚麻酸植物甾醇酯（PS-ALA）对高脂肪饮食喂养的小鼠和油酸诱导的肝细胞中 ERS 触发的细胞凋亡的保护作用，并进一步探讨其潜在机制。我们的结果表明，PS-ALA 可改善体内和体外模型中的非酒精性脂肪性肝病（NAFLD）。此外，PS-ALA 通过抑制 IRE1α/TRAF2/JNK 信号通路，减轻 ERS 及相关凋亡。此外，我们发现 PS-ALA 对 ERS 触发的细胞凋亡的保护作用是通过激活 AMP 激活的蛋白激酶（AMPK）介导的，因为用 AMPK 抑制剂 Compound C 预处理会消除 PS-ALA 的抗凋亡作用。总之，我们的研究结果表明，PS-ALA 通过激活 AMPK 来减轻 ERS 介导的细胞凋亡，这为 PS-ALA 在 NAFLD 中的保护作用提供了新的见解。
