Xu Yahui, Zhang Jie, Zhang Ting, Zi Minghui, Zhang Qiao
Yunnan Provincial Key Laboratory of Public Health and Biosafety & School of Public Health, Kunming Medical University, Kunming, Yunnan, China.
PPAR Res. 2024 Dec 20;2024:7178801. doi: 10.1155/ppar/7178801. eCollection 2024.
Hyperlipidemia is a critical risk factor for obesity, diabetes, cardiovascular diseases, and other chronic diseases. Our study was to determine the effects and mechanism of mangiferin (MF) and epigallocatechin gallate (EGCG) compounds on improving hyperlipidemia in HepG2 cells. HepG2 cells were treated with 0.25 mM palmitic acid (PA) and then incubated with MF (12.5, 25, and 50 M) or EGCG (25, 50, and 100 M) or MF:EGCG (0:0, 6.25:12.5, 25:50, and 50:100 M:M) for 24 h. The improvement of hyperlipidemia was verified by Oil Red O staining, changes in triglyceride (TG) and free fatty acid (FFA) levels, and the expression of lipid metabolizing proteins in western blotting. MF (12.5, 25, and 50 M) or EGCG (25, 50, and 100 M) markedly lowered lipid accumulations by lipid index levels. Furthermore, we found that the optimum concentration of MF and EGCG compounds was 25:50 (M:M), which significantly reduced the FFA level, TG, and total cholesterol (TC) accumulations and increased FFA uptake in HepG2 cells, and the effect was better than that of single phytochemicals. The adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) protein and its downstream proteins sirtuin 1 (SIRT1), peroxisome proliferator-activated receptor (PPAR), and those involved in fatty acid translocase (CD36) and carnitine palmitoyltransferase 1 (CPT1) were also markedly increased in HepG2 cells. The upregulation of protein expression was reversed when AMPK-specific inhibitor Compound C was added. MF and EGCG (25:50 M) compounds protect against hyperlipidemia by promoting the FFA oxidation, alleviating TG and TC accumulations via the AMPK/PPAR pathway in PA-treated HepG2 cells.
高脂血症是肥胖、糖尿病、心血管疾病和其他慢性疾病的关键危险因素。我们的研究旨在确定芒果苷（MF）和表没食子儿没食子酸酯（EGCG）化合物对改善HepG2细胞高脂血症的作用及机制。用0.25 mM棕榈酸（PA）处理HepG2细胞，然后分别与MF（12.5、25和50 μM）或EGCG（25、50和100 μM）或MF:EGCG（0:0、6.25:12.5、25:50和50:100 μM:μM）孵育24小时。通过油红O染色、甘油三酯（TG）和游离脂肪酸（FFA）水平的变化以及蛋白质免疫印迹法中脂质代谢相关蛋白的表达来验证高脂血症的改善情况。MF（12.5、25和50 μM）或EGCG（25、50和100 μM）通过脂质指数水平显著降低脂质积累。此外，我们发现MF和EGCG化合物的最佳浓度为25:50（μM:μM），其显著降低了HepG2细胞中的FFA水平、TG和总胆固醇（TC）积累，并增加了FFA摄取，且效果优于单一植物化学物质。腺苷5'-单磷酸（AMP）激活的蛋白激酶（AMPK）蛋白及其下游蛋白沉默调节蛋白1（SIRT1）、过氧化物酶体增殖物激活受体（PPAR）以及参与脂肪酸转位酶（CD36）和肉碱棕榈酰转移酶1（CPT1）的蛋白在HepG2细胞中也显著增加。当加入AMPK特异性抑制剂化合物C时，蛋白表达的上调被逆转。MF和EGCG（25:50 μM）化合物通过促进FFA氧化，在PA处理的HepG2细胞中通过AMPK/PPAR途径减轻TG和TC积累，从而预防高脂血症。
