Shandong Provincial Key Laboratory of Animal Resistant Biology, College of Life Sciences, Shandong Normal University, Jinan, China.
Department of Radiologic Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand.
Adipocyte. 2020 Dec;9(1):24-34. doi: 10.1080/21623945.2020.1721235.
Insulin plays an important role during adipogenic differentiation of animal preadipocytes and the maintenance of mature phenotypes. However, its role and mechanism in dedifferentiation of adipocyte remains unclear. This study investigated the effects of insulin on dedifferentiation of mice adipocytes, and the potential mechanisms. The preadipocytes were isolated from the subcutaneous white adipose tissue of wild type (WT), TNFα gene mutant (TNFα-/-), leptin gene spontaneous point mutant () and TNFα-/-/ mice and were then induced for differentiation. Interestingly, dedifferentiation of these adipocytes occurred once removing exogenous insulin from the adipogenic medium. As characteristics of dedifferentiation of the adipocytes, downregulation of adipogenic markers, upregulation of stemness markers and loss of intracellular lipids were observed from the four genotypes. Notably, dedifferentiation was occurring earlier if the insulin signal was blocked. These dedifferentiated cells regained the potentials of the stem cell-like characteristics. There is no significant difference in the characteristics of the dedifferentiation between the adipocytes. Overall, the study provided evidence that insulin plays a negative regulatory role in the dedifferentiation of adipocytes. We also confirmed that both dedifferentiation of mouse adipocytes, and effect of the insulin on this process were independent of the cell genotypes, while it is a widespread phenomenon in the adipocytes.
胰岛素在动物前体脂肪细胞的成脂分化和成熟表型的维持中起着重要作用。然而，其在脂肪细胞去分化中的作用和机制尚不清楚。本研究探讨了胰岛素对小鼠脂肪细胞去分化的影响及其潜在机制。从野生型（WT）、肿瘤坏死因子α基因突变型（TNFα-/-）、瘦素基因自发点突变型（）和 TNFα-/-/小鼠的皮下白色脂肪组织中分离前体脂肪细胞，并诱导其分化。有趣的是，一旦从成脂培养基中去除外源性胰岛素，这些脂肪细胞就会发生去分化。作为脂肪细胞去分化的特征，四种基因型的脂肪细胞中，成脂标志物下调，干性标志物上调，细胞内脂质丢失。值得注意的是，如果阻断胰岛素信号，去分化更早发生。这些去分化的细胞恢复了类似干细胞的特征潜力。脂肪细胞的去分化特征没有明显差异。总的来说，本研究提供了证据表明胰岛素在脂肪细胞的去分化中起负调控作用。我们还证实，小鼠脂肪细胞的去分化以及胰岛素对这一过程的影响独立于细胞基因型，而这是脂肪细胞中的普遍现象。
