Coplanar polychlorinated biphenyls impair glucose homeostasis in lean C57BL/6 mice and mitigate beneficial effects of weight loss on glucose homeostasis in obese mice.
Coplanar polychlorinated biphenyls impair glucose homeostasis in lean C57BL/6 mice and mitigate beneficial effects of weight loss on glucose homeostasis in obese mice.
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DOI：
10.1289/ehp.1205421
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发表时间：
2013-01
影响因子：
10.4
通讯作者：
Cassis LA
中科院分区：
文献类型：
--
作者：
Baker NA;Karounos M;English V;Fang J;Wei Y;Stromberg A;Sunkara M;Morris AJ;Swanson HI;Cassis LA
背景：以往的研究表明，共面多氯联苯（PCBs）促进脂肪细胞中促炎基因的表达。多氯联苯具有高度亲脂性，并在脂肪组织中积累，这是2型糖尿病患者胰岛素抵抗的一个部位。目的：我们研究了体外和体内共面多氯联苯对脂肪组织肿瘤坏死因子α（TNF-α）表达以及对瘦小鼠和肥胖小鼠葡萄糖和胰岛素稳态的影响。研究方法：我们定量了给予溶剂、PCB-77或PCB-126并喂食低脂（LF）饮食的雄性C57 BL/6小鼠的肝脏、肌肉和脂肪组织中的葡萄糖和胰岛素耐受性以及TNF-α水平。另一组给予载体或PCB-77的小鼠喂食高脂肪（HF）饮食12周;然后将饮食从HF转换为LF 4周以诱导体重减轻。我们对这些小鼠的葡萄糖和胰岛素耐受性以及脂肪TNF-α表达进行了定量。此外，我们使用体外和体内研究来量化PCB-77对葡萄糖稳态参数的芳烃受体（AhR）依赖性影响。结果：共面多氯联苯治疗导致持续损害的葡萄糖和胰岛素耐量的小鼠喂养LF饮食。在PCB-77处理的小鼠中，TNF-α表达在脂肪组织中增加，但在肝脏或肌肉中没有增加。脂肪组织中PCB-77水平明显高于肝脏或血清。AhR的拮抗作用消除了PCB-77的体外和体内效应。在肥胖小鼠中，PCB-77对葡萄糖稳态没有影响，但体重减轻后葡萄糖稳态受损。结论：共面多氯联苯损害葡萄糖稳态瘦小鼠和肥胖小鼠体重减轻。多氯联苯引起的TNF-α表达的脂肪特异性升高可能导致葡萄糖稳态受损。
Background: Previous studies demonstrated that coplanar polychlorinated biphenyls (PCBs) promote proinflammatory gene expression in adipocytes. PCBs are highly lipophilic and accumulate in adipose tissue, a site of insulin resistance in persons with type 2 diabetes. Objectives: We investigated the in vitro and in vivo effects of coplanar PCBs on adipose expression of tumor necrosis factor α (TNF-α) and on glucose and insulin homeostasis in lean and obese mice. Methods: We quantified glucose and insulin tolerance, as well as TNF-α levels, in liver, muscle, and adipose tissue of male C57BL/6 mice administered vehicle, PCB-77, or PCB-126 and fed a low fat (LF) diet. Another group of mice administered vehicle or PCB-77 were fed a high fat (HF) diet for 12 weeks; the diet was then switched from HF to LF for 4 weeks to induce weight loss. We quantified glucose and insulin tolerance and adipose TNF-α expression in these mice. In addition, we used in vitro and in vivo studies to quantify aryl hydrocarbon receptor (AhR)-dependent effects of PCB-77 on parameters of glucose homeostasis. Results: Treatment with coplanar PCBs resulted in sustained impairment of glucose and insulin tolerance in mice fed the LF diet. In PCB-77–treated mice, TNF-α expression was increased in adipose tissue but not in liver or muscle. PCB-77 levels were strikingly higher in adipose tissue than in liver or serum. Antagonism of AhR abolished both in vitro and in vivo effects of PCB-77. In obese mice, PCB-77 had no effect on glucose homeostasis, but glucose homeostasis was impaired after weight loss. Conclusions: Coplanar PCBs impaired glucose homeostasis in lean mice and in obese mice following weight loss. Adipose-specific elevations in TNF-α expression by PCBs may contribute to impaired glucose homeostasis.
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影响因子：
3.7
作者：
Patel CJ;Bhattacharya J;Butte AJ
通讯作者：
Butte AJ
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