Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Pabellón 2, Ciudad Universitaria, 1428, Buenos Aires, Argentina.
Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN), Universidad de Buenos Aires, CONICET, Buenos Aires, Argentina.
Mol Cell Biochem. 2018 Jan;437(1-2):37-44. doi: 10.1007/s11010-017-3093-y. Epub 2017 Jun 23.
Lead (Pb) is an environmental and industrial contaminant that still represents a public health problem. Elevated Pb exposure has been inversely correlated with femoral bone density and associated with osteoporosis. In the last years, it has been shown that inhibition of osteogenesis from mesenchymal stem cells activates adipogenesis and vice versa. In this paper, we investigated the effect of Pb on the differentiation of 3T3-L1 fibroblasts to adipocytes which is the cell model most used to study adipogenesis. After induction of differentiation, 2 days post-confluent cells re-enter the cell cycle and undergo mitotic clonal expansion (MCE) followed by expression of genes that produce the adipocyte phenotype. The presence of concentrations of Pb up to 10 μM during differentiation of 3T3-L1 fibroblasts did not interfere with MCE but enhanced the accumulation of cytosolic lipids that occur during adipogenesis, as well as, the induction of PPARγ, the master gene in adipogenesis. It is known that PPARγ upregulation is subsequent to induction of C/EBPβ and ERK activation, which are early events in adipogenesis. We found that both events were enhanced by Pb treatment. Our results support a stimulatory effect of Pb on adipogenesis which involves ERK activation and C/EBPβ upregulation prior to PPARγ and adipogenesis activation.
铅（Pb）是一种环境和工业污染物，仍然是一个公共卫生问题。铅暴露水平升高与股骨骨密度降低呈负相关，并与骨质疏松症有关。近年来，研究表明，间充质干细胞成骨分化的抑制会激活脂肪生成，反之亦然。在本文中，我们研究了铅对 3T3-L1 成纤维细胞向脂肪细胞分化的影响，3T3-L1 成纤维细胞是研究脂肪生成最常用的细胞模型。在诱导分化后，细胞在达到汇合 2 天后重新进入细胞周期，并经历有丝分裂克隆扩增（MCE），随后表达产生脂肪细胞表型的基因。在 3T3-L1 成纤维细胞分化过程中，浓度高达 10 μM 的铅的存在并不干扰 MCE，但增强了脂肪生成过程中细胞质脂质的积累，以及脂肪生成的主基因 PPARγ的诱导。众所周知，PPARγ 的上调是 C/EBPβ 的诱导和 ERK 激活之后发生的，这是脂肪生成的早期事件。我们发现，这两个事件都被铅处理增强了。我们的结果支持铅对脂肪生成的刺激作用，涉及 ERK 激活和 C/EBPβ 的上调，随后是 PPARγ 和脂肪生成的激活。
