Chronic Activation of Hepatic Nrf2 Has No Major Effect on Fatty Acid and Glucose Metabolism in Adult Mice

被引:6
作者
Brachs, Sebastian [1 ,2 ]
Winkel, Angelika F. [3 ]
Polack, James [1 ,2 ]
Tang, Hui [1 ,2 ]
Brachs, Maria [1 ,2 ]
Margerie, Daniel [3 ]
Brunner, Bodo [3 ]
Jahn-Hofmann, Kerstin [3 ]
Ruetten, Hartmut [3 ]
Spranger, Joachim [1 ,2 ]
Schmoll, Dieter [3 ]
机构
[1] Charite, Sch Med, Ctr Cardiovasc Res, Dept Endocrinol Diabet & Nutr, Berlin, Germany
[2] German Ctr Cardiovasc Res, DZHK Partner Site Berlin, Berlin, Germany
[3] Sanofi Aventis Deutschland GmbH, Ind Pk Hoechst, Frankfurt, Germany
来源
PLOS ONE | 2016年 / 11卷 / 11期
关键词
NONALCOHOLIC STEATOHEPATITIS; KEAP1/NRF2; PATHWAY; INSULIN-RESISTANCE; LIPID-METABOLISM; GENE-EXPRESSION; IN-VIVO; DELETION; STEATOSIS; DIET; LIVER;
D O I
10.1371/journal.pone.0166110
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The transcription factor NF-E2-related factor 2 (Nrf2) induces cytoprotective genes, but has also been linked to the regulation of hepatic energy metabolism. In order to assess the pharmacological potential of hepatic Nrf2 activation in metabolic disease, Nrf2 was activated over 7 weeks in mice on Western diet using two different siRNAs against kelch-like ECH-associated protein 1 (Keap1), the inhibitory protein of Nrf2. Whole genome expression analysis followed by pathway analysis demonstrated successful knock-down of Keap1 expression and induction of Nrf2-dependent genes involved in anti-oxidative stress defense and biotransformation, proving the activation of Nrf2 by the siRNAs against Keap1. Neither the expression of fatty acid-nor carbohydrate-handling proteins was regulated by Keap1 knock-down. Metabolic profiling of the animals did also not show effects on plasma and hepatic lipids, energy expenditure or glucose tolerance. The data indicate that hepatic Keap1/Nrf2 is not a major regulator of glucose or lipid metabolism in mice.
引用
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页数:19
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