Pan Zhi-Sen, Chen Yan-Ling, Tang Kai-Jia, Liu Zhang-Zhou, Liang Jia-Li, Guan Yan-Hao, Xin Xiao-Yi, Liu Chang-Hui, Shen Chuang-Peng
Department of Traditional Chinese Medicine, The First People's Hospital of Kashgar Prefecture, Kashgar, Xinjiang Uyghur Autonomous Region 844000, P.R. China.
Department of Endocrinology, The First Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405, P.R. China.
Exp Ther Med. 2023 May 15;26(1):320. doi: 10.3892/etm.2023.12019. eCollection 2023 Jul.
Pachymic acid (Pac), a major bioactive constituent of , is an antioxidant that inhibits triglyceride (TG) accumulation. To the best of our knowledge, the present study investigated for the first time whether Pac activated sirtuin 6 (SIRT6) signaling to alleviate oleic acid (OA)-palmitic acid (PA)-induced lipid metabolism disorders in mouse primary hepatocytes (MPHs). In the present study, MPHs challenged with Pac were used to test the effects of Pac on intracellular lipid metabolism. Molecular docking studies were performed to explore the potential targets of Pac in defending against lipid deposition. MPHs isolated from liver-specific SIRT6-deficient mice were subjected to OA + PA incubation and treated with Pac to determine the function and detailed mechanism. It was revealed that Pac activated SIRT6 by increasing its expression and deacetylase activity. Pa prevented OA + PA-induced lipid deposition in MPHs in a dose-dependent manner. Pac (50 µM) administration significantly reduced TG accumulation and increased fatty acid oxidation rate in OA + PA-incubated MPHs. Meanwhile, as per the results of molecular docking and relative mRNA levels, Pac activated SIRT6 and increased SIRT6 deacetylation levels. Furthermore, SIRT6 deletions in MPHs abolished the protective effects of Pac against OA + PA-induced hepatocyte lipid metabolism disorders. The present study demonstrated that Pac alleviates OA + PA-induced hepatocyte lipid metabolism disorders by activating SIRT6 signaling. Overall, SIRT6 signaling increases oxidative stress burden and promotes hepatocyte lipolysis.
茯苓酸（Pac）是茯苓的主要生物活性成分，是一种抑制甘油三酯（TG）积累的抗氧化剂。据我们所知，本研究首次探讨了Pac是否通过激活沉默调节蛋白6（SIRT6）信号通路来减轻油酸（OA）-棕榈酸（PA）诱导的小鼠原代肝细胞（MPH）脂质代谢紊乱。在本研究中，用Pac处理的MPH来测试Pac对细胞内脂质代谢的影响。进行分子对接研究以探索Pac在抵御脂质沉积中的潜在靶点。对从肝脏特异性SIRT6缺陷小鼠分离的MPH进行OA + PA孵育并用Pac处理，以确定其功能和详细机制。结果表明，Pac通过增加SIRT6的表达和脱乙酰酶活性来激活SIRT6。Pac以剂量依赖性方式预防OA + PA诱导的MPH脂质沉积。给予Pac（50µM）可显著降低OA + PA孵育的MPH中的TG积累并提高脂肪酸氧化率。同时，根据分子对接和相对mRNA水平的结果，Pac激活SIRT6并提高SIRT6的去乙酰化水平。此外，MPH中SIRT6的缺失消除了Pac对OA + PA诱导的肝细胞脂质代谢紊乱的保护作用。本研究表明，Pac通过激活SIRT6信号通路减轻OA + PA诱导的肝细胞脂质代谢紊乱。总体而言，SIRT6信号通路增加氧化应激负担并促进肝细胞脂解。
