Polychlorinated biphenyls exposure-induced insulin resistance is mediated by lipid droplet enlargement through Fsp27

Arch Toxicol. 2017 Jun;91(6):2353-2363. doi: 10.1007/s00204-016-1889-2. Epub 2016 Nov 11.


Although epidemiological and experimental studies demonstrated that polychlorinated biphenyls (PCBs) lead to insulin resistance, the mechanism underlying PCBs-induced insulin resistance has remained unsolved. In this study, we examined in vitro and in vivo effects of PCB-118 (dioxin-like PCB) and PCB-138 (non-dioxin-like PCB) on adipocyte differentiation, lipid droplet growth, and insulin action. 3T3-L1 adipocytes were incubated with PCB-118 or PCB-138 during adipocyte differentiation. For in vivo studies, C57BL/6 mice were administered PCB-118 or PCB-138 (37.5 mg/kg) by intraperitoneal injection and we examined adiposity and whole-body insulin action. PCB-118 and PCB-138 significantly promoted adipocyte differentiation and increased the lipid droplet (LD) size in 3T3-L1 adipocytes. In mice, both PCBs increased adipose mass and adipocyte size. Furthermore, both PCBs induced insulin resistance in vitro and in vivo. Expression of fat-specific protein 27 (Fsp27), which is localized to LD contact sites, was increased in PCB-treated 3T3-L1 adipocytes and mice. Depletion of Fsp27 by siRNA resulted in the inhibition of LD enlargement and attenuation of insulin resistance in PCB-treated 3T3-L1 adipocytes. An anti-diabetic drug, metformin, attenuated insulin resistance in PCB-treated 3T3-L1 adipocytes through the reduced expression of Fsp27 protein and LD size. This study suggests that PCB exposure-induced insulin resistance is mediated by LD enlargement through Fsp27.

Keywords: Fat-specific protein 27; Insulin resistance; Lipid droplet enlargement; Polychlorinated biphenyls.

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / drug effects*
  • Adipocytes / metabolism
  • Adipose Tissue / drug effects
  • Adipose Tissue / metabolism
  • Animals
  • Blood Glucose / analysis
  • Cell Culture Techniques
  • Cell Differentiation / drug effects
  • Cell Size / drug effects
  • Insulin / pharmacology
  • Insulin Resistance*
  • Lipid Droplets / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Polychlorinated Biphenyls / toxicity*
  • Proteins / genetics
  • Proteins / metabolism*
  • RNA, Small Interfering / genetics


  • Blood Glucose
  • Insulin
  • Proteins
  • RNA, Small Interfering
  • fat-specific protein 27, mouse
  • 2,3',4,4',5-pentachlorobiphenyl
  • 2,2',3',4,4',5-hexachlorobiphenyl
  • Polychlorinated Biphenyls