Department of Physiology, Medical University of Bialystok, Mickiewicz 2C Str., 15-222 Bialystok, Poland.
Nutrients. 2024 May 16;16(10):1501. doi: 10.3390/nu16101501.
Excessive lipid deposition affects hepatic homeostasis and contributes to the development of insulin resistance as a crucial factor for the deterioration of simple steatosis to steatohepatitis. So, it is essential to search for an effective agent for a new therapy for hepatic steatosis development before it progresses to the more advanced stages. Our study aimed to evaluate the potential protective effect of α-lipoic acid (α-LA) administration on the intrahepatic metabolism of sphingolipid and insulin signaling transduction in rats with metabolic dysfunction-associated steatotic liver disease (MASLD). The experiment was conducted on male Wistar rats subjected to a standard diet or a high-fat diet (HFD) and an intragastrically α-LA administration for eight weeks. High-performance liquid chromatography (HPLC) was used to determine sphingolipid content. Immunoblotting was used to measure the expression of selected proteins from sphingolipid and insulin signaling pathways. Multiplex assay kit was used to assess the level of the phosphorylated form of proteins from PI3K/Akt/mTOR transduction. The results revealed that α-LA decreased sphinganine, dihydroceramide, and sphingosine levels and increased ceramide level. We also observed an increased the concentration of phosphorylated forms of sphingosine and sphinganine. Changes in the expression of proteins from sphingolipid metabolism were consistent with changes in sphingolipid pools. Treatment with α-LA activated the PI3K/Akt/mTOR pathway, which enhanced the hepatic phosphorylation of Akt and mTOR. Based on these data, we concluded that α-lipoic acid may alleviate glucose intolerance and may have a protective influence on the sphingolipid metabolism under HFD; thus, this antioxidant appears to protect from MASLD development and steatosis deterioration.
过量的脂质沉积会影响肝脏的内稳态，并导致胰岛素抵抗，这是单纯性脂肪变性向脂肪性肝炎恶化的关键因素。因此，在脂肪性肝病进展到更严重的阶段之前，寻找一种有效的药物来治疗肝脂肪变性的发展是至关重要的。我们的研究旨在评估α-硫辛酸（α-LA）给药对代谢功能障碍相关脂肪性肝病（MASLD）大鼠肝内鞘脂代谢和胰岛素信号转导的潜在保护作用。实验在雄性 Wistar 大鼠上进行，分为标准饮食组或高脂肪饮食（HFD）组，并给予胃内 α-LA 给药 8 周。高效液相色谱（HPLC）用于测定鞘脂含量。免疫印迹用于测量鞘脂和胰岛素信号通路中选定蛋白的表达。多重检测试剂盒用于评估 PI3K/Akt/mTOR 转导的磷酸化蛋白水平。结果表明，α-LA 降低了神经酰胺、二氢神经酰胺和神经鞘氨醇的水平，增加了神经酰胺的水平。我们还观察到磷酸化形式的神经鞘氨醇和神经鞘氨醇浓度增加。鞘脂代谢蛋白的表达变化与鞘脂库的变化一致。α-LA 处理激活了 PI3K/Akt/mTOR 通路，增强了 Akt 和 mTOR 的肝磷酸化。基于这些数据，我们得出结论，α-硫辛酸可能缓解葡萄糖不耐受，并对 HFD 下的鞘脂代谢具有保护作用；因此，这种抗氧化剂似乎可以防止 MASLD 的发展和脂肪变性的恶化。
