Department of Internal Medicine, Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju, Gyeongnam, Republic of Korea.
Liver Int. 2012 Nov;32(10):1565-73. doi: 10.1111/j.1478-3231.2012.02857.x. Epub 2012 Aug 3.
Insulin resistance, oxidative stress, inflammation and innate immune system activation contribute to the development of non-alcoholic fatty liver disease (NAFLD) through steatosis and inflammation in the liver. The powerful antioxidant α-lipoic acid (ALA) has been shown to improve insulin sensitivity and suppress inflammatory responses. This study explores how ALA administration protects against NAFLD.
Otsuka Long-Evans Tokushima Fatty (OLETF) rats were divided into two groups (treated with 200 mg/kg/day of ALA or untreated) at 12 weeks of age and sacrificed at 28 weeks of age.
Serum levels of insulin, free fatty acids, total cholesterol, triglyceride, leptin, IL-6 and blood glucose were decreased in ALA-treated rats. Serum adiponectin levels were higher in ALA-treated rats. ALA treatment decreased the expression of sterol regulatory element binding protein-1 and acetyl CoA carboxylase, and increased glucose transporter-4 expression in the livers of OLETF rats. Expression of the antioxidant enzymes heme oxygenase-1 and Cu/Zn-superoxide dismutase was increased in the livers of ALA-treated rats. The lipid peroxidation marker 4-hydroxynonenal was decreased in the liver of ALA-treated rats. Proteins associated with innate immune activation (Toll-like receptor-4 and high-mobility group protein box-1) and inflammatory markers (vascular cell adhesion molecule-1, intercellular adhesion molecule-1, and cyclooxygenase-2) were decreased in the livers of ALA-treated rats.
Chronic ALA supplementation prevents NAFLD through multiple mechanisms by reducing steatosis, oxidative stress, immune activation and inflammation in the liver.
胰岛素抵抗、氧化应激、炎症和固有免疫系统的激活通过肝脏脂肪变性和炎症导致非酒精性脂肪性肝病（NAFLD）的发生。强大的抗氧化剂α-硫辛酸（ALA）已被证明可改善胰岛素敏感性并抑制炎症反应。本研究探讨了 ALA 给药如何预防 NAFLD。
12 周龄时，将 Otsuka Long-Evans Tokushima Fatty（OLETF）大鼠分为两组（每天给予 200mg/kg 的 ALA 或不给予），并在 28 周龄时处死。
ALA 治疗组大鼠血清胰岛素、游离脂肪酸、总胆固醇、甘油三酯、瘦素、IL-6 和血糖水平降低。血清脂联素水平在 ALA 治疗组大鼠中较高。ALA 治疗降低了 OLETF 大鼠肝脏中固醇调节元件结合蛋白-1 和乙酰辅酶 A 羧化酶的表达，并增加了葡萄糖转运蛋白-4 的表达。ALA 治疗组大鼠肝脏中抗氧化酶血红素加氧酶-1 和 Cu/Zn-超氧化物歧化酶的表达增加。肝脏中脂质过氧化标志物 4-羟基壬烯醛的含量在 ALA 治疗组大鼠中降低。与固有免疫激活（Toll 样受体-4 和高迁移率族蛋白 box-1）和炎症标志物（血管细胞黏附分子-1、细胞间黏附分子-1 和环氧化酶-2）相关的蛋白在 ALA 治疗组大鼠的肝脏中减少。
慢性 ALA 补充通过减少肝脏脂肪变性、氧化应激、免疫激活和炎症来预防 NAFLD，其机制多样。
