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

  • Molecular Toxicology
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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.

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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

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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).

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Authors and Affiliations

  1. Department of Anatomy and Cell Biology, Dong-A University College of Medicine, Dongdaeshin-dong 3-1, Seo-gu, Busan, 602-714, Republic of Korea

    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 Yoo

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  1. Hye Young Kim
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Kim, H.Y., Kwon, W.Y., Kim, Y.A. et al. Polychlorinated biphenyls exposure-induced insulin resistance is mediated by lipid droplet enlargement through Fsp27. Arch Toxicol 91, 2353–2363 (2017). https://doi.org/10.1007/s00204-016-1889-2

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