Department of Anatomy and Cell Biology, Dong-A University College of Medicine, Busan, 49201, Republic of Korea; Department of Anesthesiology and Pain Medicine, Gyeongsang National University Changwon Hospital, Changwon, 51472, Republic of Korea; Institute of Health Sciences, School of Medicine, Gyeongsang National University, Jinju, 52727, Republic of Korea.
Department of Anatomy and Cell Biology, Dong-A University College of Medicine, Busan, 49201, Republic of Korea.
Toxicol Lett. 2018 Aug;292:55-62. doi: 10.1016/j.toxlet.2018.04.029. Epub 2018 Apr 25.
Although epidemiological reports have shown the association between polychlorinated biphenyls (PCBs) and obesity, the molecular mechanism of PCB-induced obesity is mostly unknown. The aim of the present study was to further dissect the significance of lipid droplet (LD) enlargement in PCB-induced obesity. For this aim, we hypothesized that PCB-induced LD enlargement endows adipocytes with resistance to cell death, inhibiting the natural loss of adipocytes. Four types of PCBs were screened, and the detailed molecular mechanism was investigated by using PCB-138. We observed that PCB-138-conferred cell death resistance to hypertrophic adipocytes with enlarged LDs. We further observed that PCB-138 prevents Tumour necrosis factor-α (TNF-α)-induced apoptosis and necroptosis in 3T3-L1 adipocytes and increases the expression of anti-apoptotic proteins, including survivin, in vitro and in vivo. In addition, we demonstrated that fat-specific protein 27 (Fsp27), perilipin, and survivin endow adipocytes with resistance to TNF-α-induced cell death through sustaining enlarged LDs. Thus, the present study suggests that PCB-138-induced LD enlargement endows adipocytes with resistance to TNF-α-induced cell death and that Fsp27, perilipin, and survivin, at least in part, help adipocytes to sustain enlarged LDs, contributing to the induction of obesity.
虽然流行病学报告表明多氯联苯 (PCBs) 与肥胖之间存在关联，但 PCB 诱导肥胖的分子机制在很大程度上尚不清楚。本研究旨在进一步剖析脂滴 (LD) 增大在 PCB 诱导肥胖中的意义。为此，我们假设 PCB 诱导的 LD 增大赋予脂肪细胞抵抗细胞死亡的能力，从而抑制脂肪细胞的自然丢失。筛选了四种类型的 PCBs，并使用 PCB-138 研究了其详细的分子机制。我们观察到 PCB-138 赋予具有增大 LD 的肥大脂肪细胞抵抗细胞死亡的能力。我们进一步观察到 PCB-138 在体外和体内均可防止肿瘤坏死因子-α (TNF-α) 诱导的 3T3-L1 脂肪细胞凋亡和坏死，并增加抗凋亡蛋白（包括 survivin）的表达。此外，我们证明脂肪特异性蛋白 27 (Fsp27)、脂滴包被蛋白 ( perilipin ) 和 survivin 通过维持增大的 LD 赋予脂肪细胞抵抗 TNF-α 诱导的细胞死亡的能力。因此，本研究表明 PCB-138 诱导的 LD 增大赋予脂肪细胞抵抗 TNF-α 诱导的细胞死亡的能力，并且 Fsp27、perilipin 和 survivin 至少部分有助于脂肪细胞维持增大的 LD，从而导致肥胖的发生。
