Nanoformulated copper/zinc superoxide dismutase exerts differential effects on glucose vs lipid homeostasis depending on the diet composition possibly via altered AMPK signaling.

Nanoformulated copper/zinc superoxide dismutase exerts differential effects on glucose vs lipid homeostasis depending on the diet composition possibly via altered AMPK signaling.
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DOI:
10.1016/j.trsl.2017.08.002
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发表时间:
2017-10
期刊:
Translational research : the journal of laboratory and clinical medicine
影响因子:
--
通讯作者:
Saraswathi V
Saraswathi V
中科院分区:
其他
文献类型:
--
作者:
Natarajan G;Perriotte-Olson C;Bhinderwala F;Powers R;Desouza CV;Talmon GA;Yuhang J;Zimmerman MC;Kabanov AV;Saraswathi V

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有证据表明,超氧化物歧化酶1(SOD 1)促进葡萄糖与脂质代谢,这取决于饮食类型。我们最近报道,纳米SOD 1(纳米)改善脂质代谢,而不改变高脂肪(HF)饮食喂养的小鼠的葡萄糖稳态。在这里,我们试图确定纳米在调节正常饮食(CD)与HF饮食喂养的小鼠中的葡萄糖和脂质稳态的作用和潜在机制。给小鼠喂食CD或HF饮食(45%)10周,并每两天注射一次Nano,持续15天。与对照相比,CD+纳米治疗的小鼠的空腹葡萄糖水平较低(P<0.05)。相反,在HF+纳米处理的小鼠中,血糖没有改变,但血清甘油三酯较低。在CD的骨骼肌中,Nano减少了参与脂肪酸合成的基因,但在HF饮食喂养的小鼠中没有。AMPK可促进葡萄糖和脂质代谢,这取决于燃料的可用性,在CD喂养的小鼠中被Nano激活。此外,Nano增加了CD和HF饮食喂养小鼠中ACC(AMPK的下游靶点)的磷酸化。在葡萄糖或脂肪酸的存在下,纳米增加C2C12肌细胞中的线粒体呼吸,并且这种作用被AMPK抑制剂化合物C抑制。我们的数据表明,纳米分别促进CD和HF饮食喂养的小鼠的葡萄糖和脂质代谢,这种作用部分是通过AMPK信号转导介导的。
Evidence suggests that superoxide dismutase 1 (SOD1) promotes glucose versus lipid metabolism depending on the diet type. We recently reported that nanoformulated SOD1 (Nano) improved lipid metabolism without altering glucose homeostasis in high fat (HF) diet-fed mice. Here, we sought to determine the effects and potential mechanisms of Nano in modulating glucose and lipid homeostasis in mice fed a normal chow diet (CD) versus HF diet. Mice were fed a CD or a HF diet (45%) for 10 wk and injected with Nano once every two days for fifteen days. The fasting glucose level was lower (P<0.05) in CD+Nano-treated mice compared to control. Conversely, blood glucose was not altered but serum triglycerides were lower in HF+Nano-treated mice. Genes involved in fatty acid synthesis were reduced by Nano in the skeletal muscle of CD but not of HF diet-fed mice. AMPK, which promotes both glucose and lipid metabolism depending on the fuel availability, is activated by Nano in CD-fed mice. Moreover, Nano increased phosphorylation of ACC, a downstream target of AMPK, in both CD and HF diet-fed mice. Nano increased mitochondrial respiration in C2C12 myocytes in the presence of glucose or fatty acid and this effect is inhibited by Compound C, an AMPK inhibitor. Our data suggest that Nano promotes glucose and lipid metabolism in CD and HF diet-fed mice, respectively, and this effect is mediated partly via AMPK signaling.
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