Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy.
"Prof. Antonio Imbesi" Foundation, University of Messina,Messina, Italy.
Nat Prod Res. 2024 Mar;38(6):916-925. doi: 10.1080/14786419.2023.2207137. Epub 2023 May 2.
Obesity is a metabolic disorder with excessive body fat accumulation, increasing incidence of chronic metabolic diseases. Hypertrophic obesity is associated with local oxidative stress and inflammation. Herein, we evaluated the activity of micromolar concentrations of α-lipoic acid (ALA) on palmitic acid (PA)-exposed murine hypertrophic 3T3-L1 adipocytes, focussing on the main molecular pathways involved in adipogenesis, inflammation, and insulin resistance. ALA, starting from 1 µM, decreased adipocytes hypertrophy, reducing PA-triggered intracellular lipid accumulation, PPAR-γ levels, and FABP4 gene expression, and counteracted PA-induced intracellular ROS levels and NF-κB activation. ALA reverted PA-induced insulin resistance, restoring PI3K/Akt axis and inducing GLUT-1 and glucose uptake, showing insulin sensitizing properties since it increased their basal levels. In conclusion, this study supports the potential effects of low micromolar ALA against hypertrophy, inflammation, and insulin resistance in adipose tissue, suggesting its important role as pharmacological supplement in the prevention of conditions linked to obesity and metabolic syndrome.
肥胖是一种代谢紊乱,表现为体脂肪过度积累,慢性代谢性疾病的发病率增加。肥大性肥胖与局部氧化应激和炎症有关。在此,我们评估了在棕榈酸(PA)暴露的肥胖 3T3-L1 脂肪细胞中,毫摩尔浓度的α-硫辛酸(ALA)对细胞肥大的活性,重点关注参与脂肪生成、炎症和胰岛素抵抗的主要分子途径。从 1µM 开始,ALA 就可降低脂肪细胞的肥大,减少 PA 引发的细胞内脂质积累、PPAR-γ 水平和 FABP4 基因表达,并拮抗 PA 诱导的细胞内 ROS 水平和 NF-κB 激活。ALA 逆转了 PA 诱导的胰岛素抵抗,恢复了 PI3K/Akt 轴,并诱导 GLUT-1 和葡萄糖摄取,表现出胰岛素增敏特性,因为它增加了它们的基础水平。总之,这项研究支持低毫摩尔 ALA 对脂肪组织肥大、炎症和胰岛素抵抗的潜在作用,表明其作为药理学补充在预防与肥胖和代谢综合征相关的疾病方面具有重要作用。