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Archives of Toxicology

, Volume 91, Issue 6, pp 2353–2363 | Cite as

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

  • Hye Young Kim
  • Woo Young Kwon
  • Yeon A. Kim
  • Yoo Jin Oh
  • Seung Hee Yoo
  • Mi Hwa Lee
  • Ju Yong Bae
  • Jong-Min Kim
  • Young Hyun YooEmail author
Molecular Toxicology

Abstract

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

Polychlorinated biphenyls Insulin resistance Lipid droplet enlargement Fat-specific protein 27 

Abbreviations

ADRP

Adipose differentiation-related protein

aP2

Adipocyte protein 2

C/EBPα

CCAAT/enhancer-binding protein alpha

eWAT

Epididymal white adipose tissue

Fsp27

Fat-specific protein 27

GTT

Glucose tolerance tests

IRβ

Insulin receptor beta

IRS1

Insulin receptor substrate 1

ITT

Insulin tolerance tests

LD

Lipid droplets

PCBs

Polychlorinated biphenyls

PI3K

Phosphoinositide 3-kinase

PPARγ

Peroxisome proliferator-activated receptor gamma

Notes

Acknowledgements

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.

Ethical standards

The manuscript does not contain clinical studies or participant data.

Supplementary material

204_2016_1889_MOESM1_ESM.pdf (136 kb)
Supplementary material 1 (PDF 135 kb)
204_2016_1889_MOESM2_ESM.pdf (200 kb)
Supplementary material 2 (PDF 199 kb)
204_2016_1889_MOESM3_ESM.pdf (52 kb)
Supplementary material 3 (PDF 52 kb)
204_2016_1889_MOESM4_ESM.pdf (217 kb)
Supplementary material 4 (PDF 217 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Hye Young Kim
    • 1
  • Woo Young Kwon
    • 1
  • Yeon A. Kim
    • 1
  • Yoo Jin Oh
    • 1
  • Seung Hee Yoo
    • 1
  • Mi Hwa Lee
    • 1
  • Ju Yong Bae
    • 1
  • Jong-Min Kim
    • 1
  • Young Hyun Yoo
    • 1
    Email author
  1. 1.Department of Anatomy and Cell BiologyDong-A University College of MedicineBusanRepublic of Korea

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