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

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

Author information

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.
2
Department of Anatomy and Cell Biology, Dong-A University College of Medicine, Dongdaeshin-dong 3-1, Seo-gu, Busan, 602-714, Republic of Korea. yhyoo@dau.ac.kr.

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:

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

PMID:
27837308
DOI:
10.1007/s00204-016-1889-2
[Indexed for MEDLINE]

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