期刊
FREE RADICAL BIOLOGY AND MEDICINE
卷 61, 期 -, 页码 85-94出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2013.03.007
关键词
Nrf2; Keap1; Steatosis; Metabolic syndrome; Free radicals
资金
- National Institutes of Health [1R01ES016042, 5K22ES013782]
- National Center for Research Resources [5P20RR016457-11]
- Institute for General Medical Science components of the National Institutes of Health [8P20 GM103430-11]
- Society of Toxicology Association of Scientists of Indian Origin
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 contributions of Nrf2 to other cellular functions, such as lipid homeostasis, are emerging. This study was conducted to determine how enhanced Nrf2 activity influences the 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, and monocyte chemoattractant protein 1 mRNA expression, as well as increased acetyl-CoA carboxylase 1 and stearoyl-CoA desaturase-1 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 downregulation 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. (C) 2013 Elsevier Inc. All rights reserved.
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