Effects of Adipocyte Aryl Hydrocarbon Receptor Deficiency on PCB-Induced Disruption of Glucose Homeostasis in Lean and Obese Mice.
Effects of Adipocyte Aryl Hydrocarbon Receptor Deficiency on PCB-Induced Disruption of Glucose Homeostasis in Lean and Obese Mice.
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DOI：
10.1289/ehp.1408594
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发表时间：
2015-10
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;Shoemaker R;English V;Larian N;Sunkara M;Morris AJ;Walker M;Yiannikouris F;Cassis LA
共面多氯联苯（PCB）促进脂肪细胞炎症和损害葡萄糖稳态瘦小鼠。亲脂性多氯联苯的促糖尿病效应仅在肥胖小鼠体重减轻期间观察到。将多氯联苯暴露与葡萄糖代谢受损联系起来的分子机制尚不清楚。在这项研究中，我们测试的假设，共面多氯联苯脂肪细胞芳烃受体（AhRs）的行为，以促进脂肪炎症和损害葡萄糖稳态瘦小鼠和肥胖小鼠在减肥。PCB-77给药在LF（低脂饮食）喂养的对照（AhRfl/fl）小鼠中损害葡萄糖和胰岛素耐受性，但在脂肪细胞AhR缺陷小鼠（AhRAdQ）中不损害。出乎意料的是，AhRAdQ小鼠在喂食标准LF或高脂肪（HF）饮食时表现出增加的脂肪量。在喂食HF饮食的小鼠中，两种基因型都变得肥胖，但与AhRfl/fl对照相比，施用媒介物（VEH）的AhRAdQ小鼠表现出增加的体重、脂肪量、脂肪炎症和葡萄糖耐量受损。在两种基因型的肥胖小鼠中均未观察到PCB-77对葡萄糖稳态的损害。然而，体重减轻后，与给予VEH的小鼠相比，给予PCB-77的AhRfl/fl小鼠显示脂肪肿瘤坏死因子-α（TNF-α）mRNA丰度增加，葡萄糖稳态受损。相比之下，PCB-77对体重减轻的AhRAdQ小鼠的TNF-α或葡萄糖稳态没有影响。我们的研究结果表明，脂肪细胞AhR介导的PCB诱导的脂肪炎症和损害的葡萄糖稳态小鼠。此外，AhR在脂肪细胞中的缺乏增加了肥胖的发展，表明AhR的内源性配体调节脂肪稳态。Baker NA，Shoemaker R，English V，Larian N，Sunkara M，Morris AJ，步行者M，Yiannikouris F，Coffee LA. 2015.脂肪细胞芳烃受体缺陷对多氯联苯诱导的瘦和肥胖小鼠葡萄糖稳态破坏的影响。环境健康展望123：944-950; http：dx.doi.org/10.1289/ehp.1408594
Coplanar polychlorinated biphenyls (PCBs) promote adipocyte inflammation and impair glucose homeostasis in lean mice. The diabetes-promoting effects of lipophilic PCBs have been observed only during weight loss in obese mice. The molecular mechanisms linking PCB exposures to impaired glucose metabolism are unclear. In this study we tested the hypothesis that coplanar PCBs act at adipocyte aryl hydrocarbon receptors (AhRs) to promote adipose inflammation and impair glucose homeostasis in lean mice and in obese mice during weight loss. PCB-77 administration impaired glucose and insulin tolerance in LF (low fat diet)–fed control (AhRfl/fl) mice but not in adipocyte AhR–deficient mice (AhRAdQ). Unexpectedly, AhRAdQ mice exhibited increased fat mass when fed a standard LF or high fat (HF) diet. In mice fed a HF diet, both genotypes became obese, but AhRAdQ mice administered vehicle (VEH) exhibited increased body weight, adipose mass, adipose inflammation, and impaired glucose tolerance compared with AhRfl/fl controls. Impairment of glucose homeostasis in response to PCB-77 was not observed in obese mice of either genotype. However, upon weight loss, AhRfl/fl mice administered PCB-77 exhibited increased abundance of adipose tumor necrosis factor-α (TNF-α) mRNA and impaired glucose homeostasis compared with those administered VEH. In contrast, PCB-77 had no effect on TNF-α or glucose homeostasis in AhRAdQ mice exhibiting weight loss. Our results demonstrate that adipocyte AhR mediates PCB-induced adipose inflammation and impairment of glucose homeostasis in mice. Moreover, deficiency of AhR in adipocytes augmented the development of obesity, indicating that endogenous ligand(s) for AhR regulate adipose homeostasis. Baker NA, Shoemaker R, English V, Larian N, Sunkara M, Morris AJ, Walker M, Yiannikouris F, Cassis LA. 2015. Effects of adipocyte aryl hydrocarbon receptor deficiency on PCB-induced disruption of glucose homeostasis in lean and obese mice. Environ Health Perspect 123:944–950; http://dx.doi.org/10.1289/ehp.1408594