Polychlorinated biphenyl congener 180 (PCB 180) regulates mitotic clonal expansion and enhances adipogenesis through modulation of C/EBP beta SUMOylation in preadipocytes
Polychlorinated biphenyl congener 180 (PCB 180) regulates mitotic clonal expansion and enhances adipogenesis through modulation of C/EBP beta SUMOylation in preadipocytes
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多氯联苯同源物 180 (PCB 180) 通过调节前脂肪细胞中的 C/EBP beta SUMOylation 来调节有丝分裂克隆扩张并增强脂肪生成
DOI：
10.1016/j.fct.2021.112205
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发表时间：
2021
影响因子：
4.3
通讯作者：
Xie Xinni
中科院分区：
文献类型：
--
作者：
Yu Caixia;Wen Qing;Ren Qidong;Du Yuguo;Xie Xinni
PCB 180是典型的非二恶英类多氯联苯（NDL-PCB）。它是在人体脂肪组织中发现的最普遍的多氯联苯同系物之一。然而，PCB 180在肥胖中的作用仍然知之甚少。本研究旨在探讨PCB 180的成脂作用及其机制.当分化暴露于PCB 180的鼠3 T3-L1前脂肪细胞或人内脏前脂肪细胞（HPA-v）时，观察到脂肪形成的显著增强。此外，在前两天暴露于PCB 180对脂肪形成效应至关重要。根据从连续的细胞周期分析，细胞计数，BrdU掺入，和细胞周期蛋白D1，细胞周期蛋白B1，和p27蛋白定量的结果，PCB 180被发现在早期脂肪形成分化过程中增强有丝分裂克隆扩增（MCE）。分子机制研究表明，PCB 180促进C/EBPβ蛋白的积累，这是控制MCE的关键调节因子。最后，发现PCB 180通过上调SENP 2抑制C/EBPβ的SUMO化和随后的泛素化来减轻C/EBPβ蛋白的降解。总之，首次显示PCB 180通过减轻C/EBPβ蛋白SUMO化促进脂肪形成。这一结果为PCB 180的致肥胖作用提供了新的证据。
PCB 180 is a typical non-dioxin-like polychlorinated biphenyl (NDL-PCB). It is one of the most prevalent PCB-congeners found in human adipose tissue. However, the role of PCB 180 in obesity remains poorly understood. The aim of this study was to explore the adipogenic effect and mechanism of PCB 180. Significant enhancement in adipogenesis was observed when differentiating murine 3T3-L1 preadipocytes or human preadipocytes-visceral (HPA-v) that were exposed to PCB 180. Furthermore, exposure to PCB 180 during the first two days was critical to the adipogenic effect. According to results from sequential cell cycle analyses, cell counting, BrdU incorporation, and cyclin D1, cyclin B1, and p27 protein quantification, PCB 180 was found to enhance mitotic clonal expansion (MCE) during early adipogenic differentiation. Molecular mechanistic investigation revealed that PCB 180 promoted accumulation of the C/EBPβ protein, a key regulator that controls MCE. Finally, it was found that PCB 180 mitigated degradation of the C/EBPβ protein by repressing the SUMOylation and subsequent ubiquitination of C/EBPβ by the upregulation of SENP2. In summary, it was shown for the first time that PCB 180 facilitated adipogenesis by alleviating C/EBPβ protein SUMOylation. This result provides novel evidence regarding obesogenic effect of PCB 180.