Synthesis of cytochrome c oxidase 1 (SCO1) inhibits insulin sensitivity by decreasing copper levels in adipocytes
Synthesis of cytochrome c oxidase 1 (SCO1) inhibits insulin sensitivity by decreasing copper levels in adipocytes
复制标题
细胞色素 C 氧化酶 1 (SCO1) 的合成通过降低脂肪细胞中的铜水平来抑制胰岛素敏感性
DOI：
10.1016/j.bbrc.2017.06.124
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发表时间：
2017
影响因子：
3.1
通讯作者：
Tang Qi Qun
中科院分区：
文献类型：
--
作者：
Wei Xiang bo;Guo Liang;Liu Yang;Zhou Shui rong;Liu Yuan;Dou Xin;Du Shao yue;Ding Meng;Peng Wan qiu;Qian Shu wen;Huang Hai yan;Tang Qi Qun
胰岛素信号失调导致2型糖尿病（T2DM）和其他代谢紊乱。肥胖是胰岛素抵抗的重要因素，尽管近年来对这一关系的认识有所提高，但肥胖诱导胰岛素抵抗的机制尚不完全清楚。铜代谢紊乱往往伴随着肥胖的发展，这增加了胰岛素抵抗的风险。细胞色素氧化酶1 （SCO1）的合成在细胞色素氧化酶（COX）的组装和细胞铜稳态中起作用。然而，SCO1在代谢调节中的作用尚不清楚。在这里，我们发现肥胖小鼠在白色脂肪组织（WAT）中的SCO1表达高于对照组小鼠，铜水平较低。脂肪细胞中SCO1的过表达与铜缺乏有关。铜通过降低磷酸酶和紧张素同源物（PTEN）蛋白的水平增加胰岛素敏感性。SCO1的异位表达导致胰岛素抵抗，并伴有细胞内铜水平的降低，铜的添加消除了SCO1对胰岛素敏感性的抑制作用。我们的研究结果证明了SCO1通过调节WAT中铜浓度来调节胰岛素敏感性的新作用，并提出了T2DM的潜在治疗靶点。
Dysregulation of insulin signaling leads to type 2 diabetes mellitus (T2DM) and other metabolic disorders. Obesity is an important contributor to insulin resistance, and although the understanding of this relationship has improved in recent years, the mechanism of obesity-induced insulin resistance is not completely understood. Disorders of copper metabolism tend to accompany the development of obesity, which increases the risk of insulin resistance. Synthesis of cytochromecoxidase 1 (SCO1) functions in the assembly of cytochromecoxidase (COX) and cellular copper homeostasis. However, the role of SCO1 in the regulation of metabolism remains unknown. Here, we found that obese mice had higher expression of SCO1 and lower levels of copper in white adipose tissue (WAT) than did the control mice. Overexpression of SCO1 in adipocytes was associated with copper deficiency. Copper increased insulin sensitivity by decreasing the level of phosphatase and tensin homolog (PTEN) protein. Ectopic expression of SCO1 led to insulin resistance and was accompanied by a decrease in intracellular copper level, and addition of copper abolished the inhibitory effect of SCO1 on insulin sensitivity. Our results demonstrated a novel role of SCO1 in modulating insulin sensitivity via the regulation of copper concentration in WAT and suggested a potential therapeutic target for T2DM.