Dysregulation of adipose glutathione peroxidase 3 in obesity contributes to local and systemic oxidative stress
Dysregulation of adipose glutathione peroxidase 3 in obesity contributes to local and systemic oxidative stress
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DOI：
10.1210/me.2008-0023
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发表时间：
2008-09-01
影响因子：
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通讯作者：
Kim, Jae Bum
中科院分区：
文献类型：
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作者：
Lee, Yun Sok;Kim, A. Young;Kim, Jae Bum
谷胱甘肽过氧化物酶 3 (GPx3) 负责血浆中的主要抗氧化活性。在这里，我们证明肥胖受试者血浆中 GPx3 的下调与脂肪 GPx3 失调有关，这是由于炎症信号和氧化应激的增加造成的。尽管 GPx3 在肾、肺和脂肪组织中大量表达，但我们观察到，随着血浆 GPx3 水平的降低，在几种肥胖动物模型的脂肪组织中 GPx3 表达选择性降低。促氧化条件（如高水平的 TNF α 和缺氧）极大地抑制了脂肪 GPx3 的表达。相比之下，抗氧化剂 N-乙酰半胱氨酸和抗糖尿病药物罗格列酮增加了肥胖和糖尿病 db/db 小鼠的脂肪 GPx3 表达。此外，脂肪细胞中的 GPx3 过表达改善了高葡萄糖诱导的胰岛素抵抗并减弱了炎症基因的表达，而脂肪细胞中的 GPx3 中和则促进了促炎症基因的表达。总而言之，这些数据表明，肥胖受试者脂肪组织中 GPx3 表达的抑制可能构成恶性循环，从而扩大脂肪组织中局部活性氧的积累，可能导致全身氧化应激和肥胖相关的代谢并发症。
Glutathione peroxidase 3 (GPx3) accounts for the major antioxidant activity in the plasma. Here, we demonstrate that down-regulation of GPx3 in the plasma of obese subjects is associated with adipose GPx3 dysregulation, resulting from the increase of inflammatory signals and oxidative stress. Although GPx3 was abundantly expressed in kidney, lung, and adipose tissue, we observed that GPx3 expression was reduced selectively in the adipose tissue of several obese animal models as decreasing plasma GPx3 level. Adipose GPx3 expression was greatly suppressed by prooxidative conditions such as high levels of TNF alpha and hypoxia. In contrast, the antioxidant N-acetyl cysteine and the antidiabetic drug rosiglitazone increased adipose GPx3 expression in obese and diabetic db/db mice. Moreover, GPx3 overexpression in adipocytes improved high glucose-induced insulin resistance and attenuated inflammatory gene expression whereas GPx3 neutralization in adipocytes promoted expression of proinflammatory genes. Taken together, these data suggest that suppression of GPx3 expression in the adipose tissue of obese subjects might constitute a vicious cycle to expand local reactive oxygen species accumulation in adipose tissue potentially into systemic oxidative stress and obesity-related metabolic complications.