Department of Angiogenesis, National Medical Research Centre for Cardiology, Moscow, Russia; Center of Master's Programs, I.M.Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Moscow, Russia.
Department of Angiogenesis, National Medical Research Centre for Cardiology, Moscow, Russia.
Anal Biochem. 2021 Sep 1;628:114268. doi: 10.1016/j.ab.2021.114268. Epub 2021 Jun 6.
In the modern world obesity and insulin resistance contribute to a high impact on the structure of mortality. Basic research and pharmacological screenings for the search of new targets and insulin sensitizers require relevant cell models of adipocytes. Today the 3T3-L1 preadipocytes cell line is a widely used mouse-based model for investigation of adipocyte biology. Nonetheless, animal studies cannot be transferred directly in human research and nowadays the search for relevant and renewable cell models of human adipocyte is of undeniable importance. In the present study, we have compared pooled culture of human adipose-derived stem cells (ADSC) with immortalized ADSC cell line ASC52Telo. Both cell types had mesenchymal stem cell phenotype verified by flow cytometry. However, the efficacy of adipogenic differentiation, stimulation of FABP4 and PPARg protein expressions, and glucose uptake stimulation by insulin were reduced for ASC52Telo-derived adipocytes in comparison with ADSC-derived adipocytes. In addition, the analysis of insulin signaling has shown impaired phosphorylation of IRS1 and AS160 in ASC52Telo-derived cells. In summary, we have shown that immortalized cell line of human ADSC ASC52Telo have mesenchymal stem cell phenotype. Nevertheless, ASC52Telo-derived adipocytes demonstrate impaired adipogenesis and insulin sensitivity that are the main properties of healthy adipocytes.
在现代世界,肥胖症和胰岛素抵抗对死亡率的结构有很大影响。为了寻找新的靶点和胰岛素增敏剂,基础研究和药物筛选需要相关的脂肪细胞模型。如今,3T3-L1 前体脂肪细胞系是一种广泛用于研究脂肪细胞生物学的基于小鼠的模型。尽管如此,动物研究不能直接转化为人类研究,而如今,寻找相关的、可再生的人类脂肪细胞模型具有不可否认的重要性。在本研究中,我们比较了人脂肪来源干细胞(ADSC)的混合培养与永生化 ADSC 细胞系 ASC52Telo。两种细胞类型均通过流式细胞术验证了间充质干细胞表型。然而,与 ADSC 衍生的脂肪细胞相比,ASC52Telo 衍生的脂肪细胞的成脂分化效率、FABP4 和 PPARg 蛋白表达的刺激以及胰岛素刺激的葡萄糖摄取均降低。此外,胰岛素信号分析表明,ASC52Telo 衍生细胞中 IRS1 和 AS160 的磷酸化受损。总之,我们已经表明,人 ADSC 的永生化细胞系 ASC52Telo 具有间充质干细胞表型。然而,ASC52Telo 衍生的脂肪细胞表现出成脂能力受损和胰岛素敏感性降低,这是健康脂肪细胞的主要特征。