A possible inflammatory role of twist1 in human white adipocytes.
A possible inflammatory role of twist1 in human white adipocytes.
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作者：
Pettersson AT;Laurencikiene J;Mejhert N;Näslund E;Bouloumié A;Dahlman I;Arner P;Rydén M
Twist1 是一种转录因子，在小鼠棕色和白色脂肪组织 (WAT) 中高表达，并对小鼠的脂肪酸氧化产生负调节作用。 Twist1 在 WAT 中的作用尚不清楚，因此进行了研究。通过实时定量PCR测定脂肪组织内不同组织和不同细胞类型中twist1的表达。在人脂肪细胞中测定了twist1小干扰RNA对脂肪酸氧化、脂解、脂肪因子分泌和mRNA表达的影响。通过染色质免疫沉淀 (ChIP) 和报告基因检测研究了 twin1 与人类脂肪细胞中特定启动子之间的相互作用。与其他组织相比，Twist1 在人类 WAT 中高度表达，并且主要存在于脂肪细胞中。 Twist1 水平在人前脂肪细胞体外分化过程中增加。人白色脂肪细胞中twist1的基因沉默对脂肪分解或葡萄糖转运没有影响。出乎意料的是，与小鼠实验结果相反，twist1 RNA 干扰减少了脂肪酸氧化。此外，twis1沉默可下调炎症因子肿瘤坏死因子-α、白介素-6和单核细胞趋化蛋白-1的表达和分泌。 ChIP 和报告基因检测证实了 twin1 与这些基因启动子的相互作用。 Twist1可能在人类WAT炎症中发挥作用，因为它可以通过白色脂肪细胞中的直接转录作用调节炎症脂肪因子的表达和分泌。此外，与小鼠中的发现相反，twist1 可能是人类白色脂肪细胞中脂肪酸氧化的正调节因子。
Twist1 is a transcription factor that is highly expressed in murine brown and white adipose tissue (WAT) and negatively regulates fatty acid oxidation in mice. The role of twist1 in WAT is not known and was therefore examined. The expression of twist1 was determined by quantitative real-time PCR in different tissues and in different cell types within adipose tissue. The effect of twist1 small interfering RNA on fatty acid oxidation, lipolysis, adipokine secretion, and mRNA expression was determined in human adipocytes. The interaction between twist1 and specific promoters in human adipocytes was investigated by chromatin immunoprecipitation (ChIP) and reporter assays. Twist1 was highly expressed in human WAT compared with a set of other tissues and found predominantly in adipocytes. Twist1 levels increased during in vitro differentiation of human preadipocytes. Gene silencing of twist1 in human white adipocytes had no effect on lipolysis or glucose transport. Unexpectedly, and in contrast with results in mice, twist1 RNA interference reduced fatty acid oxidation. Furthermore, the expression and secretion of the inflammatory factors tumor necrosis factor-α, interleukin-6, and monocyte chemoattractant protein-1 were downregulated by twist1 silencing. ChIP and reporter assays confirmed twist1 interaction with the promoters of these genes. Twist1 may play a role in inflammation of human WAT because it can regulate the expression and secretion of inflammatory adipokines via direct transcriptional effects in white adipocytes. Furthermore, twist1 may, in contrast to findings in mice, be a positive regulator of fatty acid oxidation in human white adipocytes.