title: Polychlorinated biphenyls exposure-induced insulin resistance is mediated by lipid droplet enlargement through Fsp27.
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.
authors.affiliation: Department of Anatomy and Cell Biology, Dong-A University College of Medicine, Dongdaeshin-dong 3-1, Seo-gu, Busan, 602-714, Republic of Korea.
authors.forename: Hye Young
authors.initials: HY
authors.lastname: Kim
authors.affiliation: Department of Anatomy and Cell Biology, Dong-A University College of Medicine, Dongdaeshin-dong 3-1, Seo-gu, Busan, 602-714, Republic of Korea.
authors.forename: Woo Young
authors.initials: WY
authors.lastname: Kwon
authors.affiliation: Department of Anatomy and Cell Biology, Dong-A University College of Medicine, Dongdaeshin-dong 3-1, Seo-gu, Busan, 602-714, Republic of Korea.
authors.forename: Yeon A
authors.initials: YA
authors.lastname: Kim
authors.affiliation: Department of Anatomy and Cell Biology, Dong-A University College of Medicine, Dongdaeshin-dong 3-1, Seo-gu, Busan, 602-714, Republic of Korea.
authors.forename: Yoo Jin
authors.initials: YJ
authors.lastname: Oh
authors.affiliation: Department of Anatomy and Cell Biology, Dong-A University College of Medicine, Dongdaeshin-dong 3-1, Seo-gu, Busan, 602-714, Republic of Korea.
authors.forename: Seung Hee
authors.initials: SH
authors.lastname: Yoo
authors.affiliation: Department of Anatomy and Cell Biology, Dong-A University College of Medicine, Dongdaeshin-dong 3-1, Seo-gu, Busan, 602-714, Republic of Korea.
authors.forename: Mi Hwa
authors.initials: MH
authors.lastname: Lee
authors.affiliation: Department of Anatomy and Cell Biology, Dong-A University College of Medicine, Dongdaeshin-dong 3-1, Seo-gu, Busan, 602-714, Republic of Korea.
authors.forename: Ju Yong
authors.initials: JY
authors.lastname: Bae
authors.affiliation: Department of Anatomy and Cell Biology, Dong-A University College of Medicine, Dongdaeshin-dong 3-1, Seo-gu, Busan, 602-714, Republic of Korea.
authors.forename: Jong-Min
authors.initials: JM
authors.lastname: Kim
authors.affiliation: 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.
authors.forename: Young Hyun
authors.initials: YH
authors.lastname: Yoo
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects; D048429:Cell Size / Q000187:drug effects; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance; D066292:Lipid Droplets / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: D001786:Blood Glucose; D007328:Insulin; D011506:Proteins; D034741:RNA, Small Interfering; C525805:fat-specific protein 27, mouse; C070055:2,3',4,4',5-pentachlorobiphenyl; C029790:2,2',3',4,4',5-hexachlorobiphenyl; D011078:Polychlorinated Biphenyls
keywords: Fat-specific protein 27; Insulin resistance; Lipid droplet enlargement; Polychlorinated biphenyls