Polychlorinated biphenyl 138 exposure-mediated lipid droplet enlargement endows adipocytes with resistance to TNF-α-induced cell death

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.

Keywords: Cell death resistance; Fat-specific protein 27; Lipid droplet enlargement; Polychlorinated biphenyls; Survivin.

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / drug effects*
  • Adipocytes / metabolism
  • Adipocytes / pathology
  • Animals
  • Apoptosis / drug effects*
  • Cell Size / drug effects
  • Inhibitor of Apoptosis Proteins / metabolism
  • Lipid Droplets / drug effects*
  • Lipid Droplets / metabolism
  • Lipid Droplets / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Necrosis
  • Obesity / chemically induced*
  • Obesity / metabolism
  • Obesity / pathology
  • Perilipin-1 / metabolism
  • Polychlorinated Biphenyls / toxicity*
  • Proteins / metabolism
  • Repressor Proteins / metabolism
  • Signal Transduction / drug effects
  • Survivin
  • Time Factors
  • Tumor Necrosis Factor-alpha / toxicity*


  • Birc5 protein, mouse
  • Inhibitor of Apoptosis Proteins
  • Perilipin-1
  • Proteins
  • Repressor Proteins
  • Survivin
  • Tumor Necrosis Factor-alpha
  • fat-specific protein 27, mouse
  • 2,2',3',4,4',5-hexachlorobiphenyl
  • Polychlorinated Biphenyls