Background: Exposure to coplanar polychlorinated biphenyls (PCBs) is linked to the development of insulin resistance. Previous studies suggested that PCB126 alters muscle mitochondrial function through an indirect mechanism. Since PCBs are stored in fat, we hypothesized that PCB126 alters adipokine secretion, which in turn affects muscle metabolism. Objectives: The objectives of this study were: 1) To study the impacts of PCB126 exposure on adipocyte cytokine/adipokine secretion; 2) To determine whether adipocyte-derived factors alter glucose metabolism and mitochondrial function in myotubes when exposed to PCB126; 3) To determine whether pre-established insulin resistance alters the metabolic responses of adipocytes exposed to PCB126 and the communication between adipocytes and myotubes. Method: 3T3-L1 adipocytes were exposed to PCB126 (1-100 nM) in two insulin sensitivity conditions (insulin sensitive (IS) and insulin resistant (IR) adipocytes), followed by the measurement of secreted adipokines, mitochondrial function and insulin-stimulated glucose uptake. Communication between adipocytes and myotubes was reproduced by exposing C2C12 or mouse primary myotubes to conditioned medium (CM) derived from IS or IR 3T3-L1 adipocytes exposed to PCB126. Mitochondrial function and insulin-stimulated glucose uptake were then determined in myotubes. Results: PCB126 significantly increased adipokine (adiponectin, IL-6, MCP-1, TNF-α) secretion and decreased mitochondrial function, glucose uptake and glycolysis in IR but not in IS 3T3-L1 adipocytes. Altered energy metabolism in IR 3T3-L1 adipocytes was linked to decreased phosphorylation of AMP-activated protein kinase (p-AMPK) and increased superoxide dismutase 2 levels, an enzyme involved in reactive oxygen species detoxification. Exposure of myotubes to CM from PCB126-treated IR adipocytes decreased glucose uptake, without altering glycolysis or mitochondrial function. Interestingly, p-AMPK levels were increased rather than decreased in myotubes exposed to the CM of PCB126-treated IR adipocytes. Conclusion: Taken together, these data suggest that increased adipokine secretion from IR adipocytes exposed to PCB126 may explain impaired glucose uptake in myotubes.

中文翻译：

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PCB126介导的对脂肪细胞能量代谢和脂肪因子分泌的影响可能导致肌肉细胞异常摄取葡萄糖

背景：共面多氯联苯（PCBs）的暴露与胰岛素抵抗的发展有关。先前的研究表明PCB126通过间接机制改变肌肉线粒体功能。由于多氯联苯储存在脂肪中，我们假设多氯联苯126改变了脂肪因子的分泌，进而影响了肌肉的新陈代谢。目的：本研究的目的是：1）研究PCB126暴露对脂肪细胞细胞因子/脂肪因子分泌的影响；2）确定暴露于PCB126时脂肪细胞源性因子是否会改变肌管中的葡萄糖代谢和线粒体功能；3）确定预先建立的胰岛素抵抗是否会改变暴露于PCB126的脂肪细胞的代谢反应以及脂肪细胞与肌管之间的通讯。方法：将3T3-L1脂肪细胞在两种胰岛素敏感性条件下（胰岛素敏感性（IS）和胰岛素抵抗（IR）脂肪细胞）暴露于PCB126（1-100 nM），然后测量分泌的脂肪因子，线粒体功能和胰岛素刺激的葡萄糖摄取。通过将C2C12或小鼠原代肌管暴露于衍生自暴露于PCB126的IS或IR 3T3-L1脂肪细胞的条件培养基（CM），可再现脂肪细胞与肌管之间的通讯。然后在肌管中测定线粒体功能和胰岛素刺激的葡萄糖摄取。结果：IR中的PCB126显着增加了脂肪因子（脂联素，IL-6，MCP-1，TNF-α）的分泌，并降低了线粒体功能，葡萄糖的摄取和糖酵解，但IS 3T3-L1脂肪细胞却没有。IR 3T3-L1脂肪细胞中能量代谢的改变与AMP活化蛋白激酶（p-AMPK）的磷酸化水平降低和超氧化物歧化酶2水平升高有关，而超氧化物歧化酶2水平与活性氧解毒有关。从经过PCB126处理的IR脂肪细胞向CM暴露肌管可降低葡萄糖摄取，而不改变糖酵解或线粒体功能。有趣的是，在暴露于PCB126处理的IR脂肪细胞的CM的肌管中，p-AMPK水平升高而不是降低。结论：综上所述，这些数据表明，暴露于PCB126的IR脂肪细胞中脂肪因子的分泌增加可能是肌管中葡萄糖摄取受损的原因。从经过PCB126处理的IR脂肪细胞向CM暴露肌管可降低葡萄糖摄取，而不改变糖酵解或线粒体功能。有趣的是，在暴露于PCB126处理的IR脂肪细胞的CM的肌管中，p-AMPK水平升高而不是降低。结论：综上所述，这些数据表明，暴露于PCB126的IR脂肪细胞中脂肪因子的分泌增加可能是肌管中葡萄糖摄取受损的原因。从经过PCB126处理的IR脂肪细胞向CM暴露肌管可降低葡萄糖摄取，而不改变糖酵解或线粒体功能。有趣的是，在暴露于PCB126处理的IR脂肪细胞的CM的肌管中，p-AMPK水平升高而不是降低。结论：综上所述，这些数据表明，暴露于PCB126的IR脂肪细胞中脂肪因子的分泌增加可能是肌管中葡萄糖摄取受损的原因。