Key Laboratory of Animal Physiology and Biochemistry, Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China.
MOE Joint International Research Laboratory of Animal Health & Food Safety, Nanjing Agricultural University, Nanjing 210095, China.
Nutrients. 2021 Jul 8;13(7):2331. doi: 10.3390/nu13072331.
Excessive liver lipid deposition is a vital risk factor for the development of many diseases. Here, we fed Sprague-Dawley rats with a control or α-lipoic acid-supplemented diet (0.2%) for 5 weeks to elucidate the effects of α-lipoic acid on preventive ability, hepatic lipid metabolism-related gene expression, and the involved regulatory mechanisms. In the current study, α-lipoic acid supplementation lowered plasma triglyceride level and hepatic triglyceride content. Reduced hepatic lipid deposition was closely associated with inhibiting fatty acid-binding protein 1 and fatty acid synthase expression, as well as increasing phosphorylated hormone-sensitive lipase expression at the protein level in α-lipoic acid-exposed rats. Hepatic miRNA sequencing revealed increased expression of miR-3548 targeting the 3'untranslated region of Fasn mRNA, and the direct regulatory link between miRNA-3548 and FASN was verified by dual-luciferase reporter assay. Taken together, α-lipoic acid lowered hepatic lipid accumulation, which involved changes in miRNA-mediated lipogenic genes.
肝脏脂质沉积过多是许多疾病发展的重要危险因素。在这里，我们用对照或添加α-硫辛酸（0.2%）的饮食喂养 Sprague-Dawley 大鼠 5 周，以阐明α-硫辛酸对预防能力、肝脏脂质代谢相关基因表达的影响，以及涉及的调节机制。在本研究中，α-硫辛酸补充降低了血浆甘油三酯水平和肝甘油三酯含量。肝脂质沉积减少与抑制脂肪酸结合蛋白 1 和脂肪酸合酶表达密切相关，并增加了α-硫辛酸暴露大鼠的激素敏感脂肪酶磷酸化表达。肝 miRNA 测序显示，miR-3548 对 Fasn mRNA 的 3'非翻译区的表达增加，miRNA-3548 和 FASN 之间的直接调节关系通过双荧光素酶报告实验得到验证。综上所述，α-硫辛酸降低了肝脂质堆积，这涉及到 miRNA 介导的脂肪生成基因的变化。
