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

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 W...

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Bibliographic Details
Published in:PloS one 2016-11, Vol.11 (11), p.e0166110-e0166110
Main Authors: Brachs, Sebastian, Winkel, Angelika F, Polack, James, Tang, Hui, Brachs, Maria, Margerie, Daniel, Brunner, Bodo, Jahn-Hofmann, Kerstin, Ruetten, Hartmut, Spranger, Joachim, Schmoll, Dieter
Format: Article
Language:English
Subjects:
Activation
Adaptor Proteins, Signal Transducing - metabolism
Analysis
Animals
Biology and life sciences
Biotransformation
Body composition
Carbohydrate Metabolism - physiology
Carbohydrates
Cytoskeletal Proteins - metabolism
Diabetes
Endocrinology
Energy expenditure
Energy metabolism
Fatty acids
Fatty Acids - metabolism
Gene expression
Genes
Genetic aspects
Genomes
Glucose
Glucose - metabolism
Glucose tolerance
Insulin resistance
Intracellular Signaling Peptides and Proteins - metabolism
Kelch-Like ECH-Associated Protein 1 - metabolism
Lipid metabolism
Lipid Metabolism - physiology
Lipids
Male
Medicine
Medicine and Health Sciences
Metabolic rate
Metabolism
Mice
Mice, Inbred C57BL
NF-E2-Related Factor 2 - metabolism
Nutrition research
Oxidative stress
Oxidative Stress - physiology
Pharmacology
Physiology
Proteins
Rodents
Signal Transduction - physiology
siRNA
Studies
Transcription (Genetics)
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0166110