Polychlorinated biphenyls exposure-induced insulin resistance is mediated by lipid droplet enlargement through Fsp27
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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.
KeywordsPolychlorinated biphenyls Insulin resistance Lipid droplet enlargement Fat-specific protein 27
Adipose differentiation-related protein
Adipocyte protein 2
CCAAT/enhancer-binding protein alpha
Epididymal white adipose tissue
Fat-specific protein 27
Glucose tolerance tests
Insulin receptor beta
Insulin receptor substrate 1
Insulin tolerance tests
Peroxisome proliferator-activated receptor gamma
This work was supported by the National Research Foundation of Korea (NRF) Grant funded by the Korean Government (MISP) (Nos. 2015R1A2A1A10051603, 2016R1C1B2011721, and 2016R1A5A2007009).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
The manuscript does not contain clinical studies or participant data.
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