Abstract：
BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a prevalent condition characterized by hepatic fat accumulation, often progressing to severe liver injury, for which approved treatments are currently lacking. This study explores the potential therapeutic impact of alpha-lipoic acid (ALA), a natural compound crucial in lipid metabolism, on NAFLD using an in vitro model.
METHODS: HepG2 cells were treated with a palmitic acid:oleic acid (PA:OA) mixture, representing a cellular model of steatosis. Subsequent treatment with ALA at concentrations of 1 µM and 5 µM aimed to evaluate its effects on lipid content and metabolism. Real-time polymerase chain reaction (PCR), BODIPY staining, cytofluorimetric analysis, and lipidomics were used to assess gene expression, lipid droplet accumulation, and fatty acid profiles.
RESULTS: Our results showed that ALA significantly reduced lipid droplets in PA:OA-treated HepG2 cells, with a concentration-dependent effect. Analysis of fatty acid profiles demonstrated a decrease in palmitic acid levels with ALA treatment, while oleic acid reduction was observed only at the higher concentration. Moreover, ALA modulated the expression of genes involved in cholesterol biosynthesis and low-density lipoprotein (LDL) metabolism, indicating a potential role in lipid homeostasis. Further insights into molecular mechanisms revealed that ALA modulated peroxisome proliferator activated receptors (PPARs), specifically PPAR-alpha and PPAR-gamma, involved in fatty acid metabolism and insulin sensitivity. Finally, ALA counteracted the overexpression of thermogenic genes induced by exogenous fatty acids, suggesting a regulatory role in energy dissipation pathways.
CONCLUSIONS: In conclusion, this study highlights ALA as a therapeutic agent in mitigating lipid accumulation and dysregulation in NAFLD.
METHODS: HepG2 cells were treated with a palmitic acid:oleic acid (PA:OA) mixture, representing a cellular model of steatosis. Subsequent treatment with ALA at concentrations of 1 µM and 5 µM aimed to evaluate its effects on lipid content and metabolism. Real-time polymerase chain reaction (PCR), BODIPY staining, cytofluorimetric analysis, and lipidomics were used to assess gene expression, lipid droplet accumulation, and fatty acid profiles.
RESULTS: Our results showed that ALA significantly reduced lipid droplets in PA:OA-treated HepG2 cells, with a concentration-dependent effect. Analysis of fatty acid profiles demonstrated a decrease in palmitic acid levels with ALA treatment, while oleic acid reduction was observed only at the higher concentration. Moreover, ALA modulated the expression of genes involved in cholesterol biosynthesis and low-density lipoprotein (LDL) metabolism, indicating a potential role in lipid homeostasis. Further insights into molecular mechanisms revealed that ALA modulated peroxisome proliferator activated receptors (PPARs), specifically PPAR-alpha and PPAR-gamma, involved in fatty acid metabolism and insulin sensitivity. Finally, ALA counteracted the overexpression of thermogenic genes induced by exogenous fatty acids, suggesting a regulatory role in energy dissipation pathways.
CONCLUSIONS: In conclusion, this study highlights ALA as a therapeutic agent in mitigating lipid accumulation and dysregulation in NAFLD.
摘要：
背景：非酒精性脂肪性肝病（NAFLD）是一种以肝脏脂肪积累为特征的常见病，经常进展为严重的肝损伤，目前缺乏批准的治疗方法。这项研究探讨了α-硫辛酸（ALA）的潜在治疗效果，一种对脂质代谢至关重要的天然化合物，使用体外模型对NAFLD进行研究。
方法：用棕榈酸：油酸（PA：OA）混合物处理HepG2细胞，代表脂肪变性的细胞模型。随后用浓度为1µM和5µM的ALA治疗旨在评估其对脂质含量和代谢的影响。实时聚合酶链反应（PCR），BODIPY染色,细胞荧光分析,和脂质组学用于评估基因表达，脂滴积累，和脂肪酸谱。
结果：我们的结果表明，ALA显着减少PA：OA处理的HepG2细胞中的脂滴，具有浓度依赖性效应。脂肪酸谱的分析表明，ALA治疗后棕榈酸水平降低，而仅在较高浓度下观察到油酸减少。此外，ALA调节胆固醇生物合成和低密度脂蛋白（LDL）代谢相关基因的表达，表明在脂质稳态中的潜在作用。对分子机制的进一步认识表明，ALA调节过氧化物酶体增殖物激活受体（PPARs），特别是PPAR-α和PPAR-γ，参与脂肪酸代谢和胰岛素敏感性。最后,ALA抵消了外源脂肪酸诱导的产热基因的过度表达，提示在能量耗散途径中的调节作用。
结论：结论：这项研究强调了ALA作为减轻NAFLD中脂质积累和失调的治疗剂.
方法：用棕榈酸：油酸（PA：OA）混合物处理HepG2细胞，代表脂肪变性的细胞模型。随后用浓度为1µM和5µM的ALA治疗旨在评估其对脂质含量和代谢的影响。实时聚合酶链反应（PCR），BODIPY染色,细胞荧光分析,和脂质组学用于评估基因表达，脂滴积累，和脂肪酸谱。
结果：我们的结果表明，ALA显着减少PA：OA处理的HepG2细胞中的脂滴，具有浓度依赖性效应。脂肪酸谱的分析表明，ALA治疗后棕榈酸水平降低，而仅在较高浓度下观察到油酸减少。此外，ALA调节胆固醇生物合成和低密度脂蛋白（LDL）代谢相关基因的表达，表明在脂质稳态中的潜在作用。对分子机制的进一步认识表明，ALA调节过氧化物酶体增殖物激活受体（PPARs），特别是PPAR-α和PPAR-γ，参与脂肪酸代谢和胰岛素敏感性。最后,ALA抵消了外源脂肪酸诱导的产热基因的过度表达，提示在能量耗散途径中的调节作用。
结论：结论：这项研究强调了ALA作为减轻NAFLD中脂质积累和失调的治疗剂.
