Polychlorinated biphenyl-77 induces adipocyte differentiation and proinflammatory adipokines and promotes obesity and atherosclerosis.
Polychlorinated biphenyl-77 induces adipocyte differentiation and proinflammatory adipokines and promotes obesity and atherosclerosis.
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多氯联苯77诱导脂肪细胞分化和促炎脂肪因子，并促进肥胖和动脉粥样硬化。
DOI：
10.1289/ehp.10554
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发表时间：
2008-06
影响因子：
10.4
通讯作者：
Cassis, Lisa A.
中科院分区：
文献类型：
--
作者：
Arsenescu, Violeta;Arsenescu, Razvan I.;King, Victoria;Swanson, Hollie;Cassis, Lisa A.
关键词：
肥胖是一种与心血管疾病有关的炎症性疾病，与脂肪组织的扩张有关。多氯联苯（PCB-77）是一种常见的共面多氯联苯（PCBs），由于其亲脂性在脂肪组织中积累，并随着肥胖而增加。然而，多氯联苯对脂肪细胞，肥胖症和肥胖相关的心血管疾病的影响是未知的。在这项研究中，我们研究了在体外和体内的PCB-77对脂肪细胞分化，促炎脂肪因子，脂肪细胞形态，体重，血脂和动脉粥样硬化的影响。将PCB-77或2，2 ′，4，4，5，5 ′-六氯联苯（PCB-153）与分化期或成熟期的3 T3-L1脂肪细胞共同孵育。比较了PCB-77和2，3，7，8-四氯二苯并对二恶英（TCDD）的浓度依赖效应。对于体内研究，我们用溶剂或PCB-77（49 mg/kg，腹腔注射）处理C57 BL/6野生型（WT）或芳烃受体（AhR）−/−小鼠，并检查体重增加。在单独的研究中，我们在6周内向ApoE−/−小鼠注射溶剂或PCB-77，并检查体重，脂肪细胞大小，血脂和动脉粥样硬化。低浓度的PCB-77或TCDD增加脂肪细胞分化，甘油-3-磷酸脱氢酶活性和过氧化物酶体增殖物激活受体γ的表达，而较高浓度则抑制脂肪细胞分化。PCB-77的作用可被AhR拮抗剂α-萘甲酮阻断。PCB-77促进3 T3-L1脂肪细胞表达和释放多种促炎细胞因子。给予PCB-77会增加WT小鼠的体重增加，但不会增加AhR-/-小鼠的体重增加。注射PCB-77的ApoE−/−小鼠表现出更大的体重、脂肪细胞肥大、血清血脂异常和动脉粥样硬化。我们的研究结果表明，PCB-77可能有助于肥胖和肥胖相关动脉粥样硬化的发展。
Obesity, an inflammatory condition linked to cardiovascular disease, is associated with expansion of adipose tissue. Highly prevalent coplanar polychlorinated biphenyls (PCBs) such as 3,3′,4,4′-tetrachlorobiphenyl (PCB-77) accumulate in adipose tissue because of their lipophilicity and increase with obesity. However, the effects of PCBs on adipocytes, obesity, and obesity-associated cardiovascular disease are unknown. In this study we examined in vitro and in vivo effects of PCB-77 on adipocyte differentiation, proinflammatory adipokines, adipocyte morphology, body weight, serum lipids, and atherosclerosis. PCB-77 or 2,2′,4,4,5,5′-hexachlorobiphenyl (PCB-153) was incubated with 3T3-L1 adipocytes either during differentiation or in mature adipocytes. Concentration-dependent effects of PCB-77 were contrasted with those of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). For in vivo studies, we treated C57BL/6 wild-type (WT) or aryl hydrocarbon receptor (AhR)−/− mice with vehicle or PCB-77 (49 mg/kg, by intraperitoneal injection) and examined body weight gain. In separate studies, we injected ApoE−/− mice with vehicle or PCB-77 over a 6-week period and examined body weight, adipocyte size, serum lipids, and atherosclerosis. Low concentrations of PCB-77 or TCDD increased adipocyte differentiation, glycerol–3-phosphate dehydrogenase activity, and expression of peroxisome proliferator–activated receptor γ, whereas higher concentrations inhibited adipocyte differentiation. Effects of PCB-77 were abolished by the AhR antagonist α-naphthoflavone. PCB-77 promoted the expression and release of various proinflammatory cytokines from 3T3-L1 adipocytes. Administration of PCB-77 increased body weight gain in WT but not AhR−/− mice. ApoE−/− mice injected with PCB-77 exhibited greater body weight, adipocyte hypertrophy, serum dyslipidemia, and augmented atherosclerosis. Our findings suggest that PCB-77 may contribute to the development of obesity and obesity-associated atherosclerosis.
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影响因子：
3.8
作者：
Kodavanti, PRS;Ward, TR;Tilson, HA
通讯作者：
Tilson, HA
影响因子：
120.7
作者：
Flegal, KM;Carroll, MD;Johnson, CL
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Johnson, CL
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120.7
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Hedley, AA;Ogden, CL;Flegal, KM
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Flegal, KM
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1.9
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Bolger, PM
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8.2
作者：
Lee, D.-H.;Lee, I.-K.;Jacobs, D. R., Jr.
通讯作者：
Jacobs, D. R., Jr.