Keap1 knockdown increases markers of metabolic syndrome after long-term high fat diet feeding.
Keap1 knockdown increases markers of metabolic syndrome after long-term high fat diet feeding.
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DOI：
10.1016/j.freeradbiomed.2013.03.007
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发表时间：
2013-08
影响因子：
7.4
通讯作者：
Slitt, Angela L.
中科院分区：
文献类型：
--
作者：
More, Vijay R.;Xu, Jialin;Shimpi, Prajakta C.;Belgrave, Clyde;Luyendyk, James P.;Yamamoto, Masayuki;Slitt, Angela L.
核因子-E2相关因子2（Nrf 2）-Kelch样ECH相关蛋白1（Keap 1）途径上调抗氧化剂和生物转化酶的表达，以对抗细胞氧化应激。Nrf 2对其他细胞功能（如脂质稳态）的贡献正在出现。本研究旨在确定Nrf 2活性增强如何影响长期高脂饮食（HFD）喂养的代谢综合征进展。C57 BL/6和Keap 1-Knockdown（Keap 1-KD）小鼠表现出增强的Nrf 2活性，喂食HFD 24周。与接受HFD的C57 BL/6小鼠相比，Keap 1-KD小鼠具有更高的体重和白色脂肪组织质量，沿着增加的炎症和脂肪生成基因表达。与C57 BL/6小鼠相比，HFD喂养在更大程度上增加了Keap 1-KD小鼠的肝脏脂肪变性和炎症，这与肝脏Cd 36、脂肪酸结合蛋白4（Fabp 4）和单核细胞趋化蛋白1（Mcp 1）mRNA表达增加以及乙酰辅酶A羧化酶1（Acc 1）和甾醇辅酶A去饱和酶1（Scd 1）蛋白表达增加有关。与C57 BL/6小鼠相比，HFD在更大程度上改变了Keap-KD小鼠的短期葡萄糖稳态，这伴随着骨骼肌中胰岛素受体底物1 mRNA表达的下调。总之，结果表明，在用HFD治疗时，Keap 1敲低增加了代谢综合征的某些标志物。
The Nuclear factor-E2 related factor 2 (Nrf2)-Kelch-like ECH-associated protein 1 (Keap1) pathway upregulates antioxidant and biotransformation enzyme expression to counter cellular oxidative stress. The contribution of Nrf2 to other cellular functions, such as lipid homeostasis is emerging. The present study was conducted to determine how enhanced Nrf2 activity impacts progression of metabolic syndrome with long-term high fat diet (HFD) feeding. C57BL/6 and Keap1-Knockdown (Keap1-KD) mice, which exhibit enhanced Nrf2 activity, were fed a HFD for 24 weeks. Keap1-KD mice had higher body weight and white adipose tissue mass compared to C57BL/6 mice on HFD, along with increased inflammation and lipogenic gene expression. HFD feeding increased hepatic steatosis and inflammation to a greater extent in Keap1-KD mice compared to C57BL/6 mice, which was associated with increased liver Cd36, fatty acid binding protein 4 (Fabp4), and monocyte chemoattractant protein 1 (Mcp1) mRNA expression, as well as, increased acetyl CoA carboxylase 1 (Acc1) and Steroyl CoA desaturase 1 (Scd1) protein expression. The HFD altered short-term glucose homeostasis to a greater degree in Keap-KD mice compared to C57BL/6 mice, which was accompanied by down regulation of Insulin receptor substrate 1 mRNA expression in skeletal muscle. Together, the results indicate that Keap1 knockdown, on treatment with HFD, increases certain markers of metabolic syndrome.
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影响因子：
29.4
作者：
Lamle, Jutta;Marhenke, Silke;Vogel, Arndt
通讯作者：
Vogel, Arndt
影响因子：
64.8
作者：
Kahn, Steven E.;Hull, Rebecca L.;Utzschneider, Kristina M.
通讯作者：
Utzschneider, Kristina M.
DOI：
10.1016/j.ecl.2008.07.002
发表时间：
2008-09
影响因子：
4.5
作者：
Halberg, Nils;Wernstedt-Asterholm, Ingrid;Scherer, Philipp E.
通讯作者：
Scherer, Philipp E.
DOI：
10.1038/nri3071
发表时间：
2011-10-10
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
3.9
作者：
More, Vijay R.;Slitt, Angela L.
通讯作者：
Slitt, Angela L.