Graduate Center for Nutritional Sciences, University of Kentucky, Lexington, Kentucky 40536-0200, USA.
Environ Health Perspect. 2013 Jan;121(1):105-10. doi: 10.1289/ehp.1205421. Epub 2012 Oct 24.
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.
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.
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.
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.
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.
先前的研究表明，共面多氯联苯（PCBs）可促进脂肪细胞中促炎基因的表达。PCBs 具有很强的亲脂性，会在脂肪组织中蓄积，而脂肪组织是 2 型糖尿病患者胰岛素抵抗的部位。
我们研究了共面 PCBs 对 lean 和肥胖小鼠脂肪组织中肿瘤坏死因子-α（TNF-α）的表达以及葡萄糖和胰岛素稳态的体外和体内作用。
我们对给予 vehicle、PCB-77 或 PCB-126 并喂食低脂（LF）饮食的雄性 C57BL/6 小鼠的肝、肌肉和脂肪组织中的葡萄糖和胰岛素耐量以及 TNF-α 水平进行了量化。另一组给予 vehicle 或 PCB-77 的小鼠喂食高脂（HF）饮食 12 周；然后将饮食从 HF 切换为 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量以及脂肪 TNF-α 表达进行了量化。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。
喂食 LF 饮食的小鼠中，共面 PCBs 的治疗导致葡萄糖和胰岛素耐量持续受损。在 PCB-77 处理的小鼠中，脂肪组织中 TNF-α 的表达增加，但在肝脏或肌肉中没有增加。PCB-77 在脂肪组织中的水平明显高于肝脏或血清中的水平。AhR 拮抗剂消除了 PCB-77 的体外和体内作用。在肥胖小鼠中，PCB-77 对葡萄糖稳态没有影响，但在体重减轻后葡萄糖稳态受损。
共面 PCBs 会在 lean 小鼠和肥胖小鼠减轻体重后损害葡萄糖稳态。PCBs 引起脂肪组织中 TNF-α 表达的特异性升高可能导致葡萄糖稳态受损。
