ZAG alleviates HFD-induced insulin resistance accompanied with decreased lipid depot in skeletal muscle in mice
ZAG alleviates HFD-induced insulin resistance accompanied with decreased lipid depot in skeletal muscle in mice
复制标题
ZAG 减轻 HFD 诱导的小鼠胰岛素抵抗并伴随骨骼肌脂质储量减少
DOI：
10.1194/jlr.m082180
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发表时间：
2018-12-01
影响因子：
6.5
通讯作者：
Yang, Xiao-Jing
中科院分区：
文献类型：
--
作者：
Gao, Shi-Xing;Guo, Jun;Yang, Xiao-Jing
在过去的二十年里，肌内脂质被认为是胰岛素抵抗的原因，因为它们能够抑制骨骼肌中胰岛素刺激的葡萄糖摄取。锌-2-糖蛋白（ZAG）是一种脂肪因子，参与白色脂肪组织（WAT）的脂解。为了研究ZAG对由影响肌内脂肪的高脂饮食（HFD）诱导的胰岛素抵抗的作用，将小鼠分为三组，正常饮食、HFD和HFD下的ZAG治疗（HFZ）。结果表明，ZAG处理的小鼠的胰岛素敏感性显著提高。与HFD组相比，HFZ组的体重、WAT重量和肌内脂肪显著降低。与HFD组相比，接受ZAG治疗的小鼠骨骼肌中的脂解酶，包括脂肪敏感性脂肪酶和脂肪甘油三酯脂肪酶的磷酸化，显著上调。胰岛素信号蛋白，如磷酸化的胰岛素受体底物1和细胞膜葡萄糖转运蛋白4型，也显着增加在骨骼肌的ZAG治疗组。此外，代谢率研究表明，ZAG过表达增加呼吸交换率和产热。在体外，ZAG处理促进葡萄糖摄取并减少C2 C12肌管中的细胞内脂质。综上所述，这些数据表明，ZAG的过表达减轻了HFD诱导的小鼠胰岛素抵抗，沿着骨骼肌脂质含量的降低。
Over the past two decades, intramuscular lipids have been viewed as a cause of insulin resistance due to their ability to suppress insulin-stimulated glucose uptake in skeletal muscle. Zinc-2-glycoprotein (ZAG) is an adipokine involved in lipolysis of white adipose tissue (WAT). To investigate the action of ZAG on insulin resistance induced by a high-fat diet (HFD), which affects the intramuscular fat, mice were divided into three groups, normal diet, HFD, and ZAG treatment under HFD (HFZ). The results showed that the insulin sensitivity of ZAG-treated mice was significantly improved. The body weight, WAT weight, and intramuscular fat were significantly decreased in the HFZ group compared with the HFD group. The lipolytic enzymes, including phosphorylation of hormone-sensitive lipase and adipose triglyceride lipase, were significantly upregulated in the skeletal muscle of mice that received the ZAG treatment compared with the HFD group. Insulin signaling proteins, such as phosphorylation of insulin receptor substrate 1 and cell membrane glucose transporter type 4, were also significantly increased in the skeletal muscle of the ZAG-treated group. Furthermore, a metabolic rate study showed that ZAG overexpression increases the respiratory exchange ratio and heat production. In vitro, ZAG treatment promotes glucose uptake and decreases intracellular lipids in C2C12 myotubes. Taken together, these data showed that overexpression of ZAG alleviates HFD-induced insulin resistance in mice, along with decreasing the lipid content of skeletal muscle.