Nrf2 represses FGF21 during long-term high-fat diet-induced obesity in mice.

Details

Serval ID
serval:BIB_BCF8EA8299B9
Type
Article: article from journal or magazin.
Collection
Publications
Title
Nrf2 represses FGF21 during long-term high-fat diet-induced obesity in mice.
Journal
Diabetes
Author(s)
Chartoumpekis D.V., Ziros P.G., Psyrogiannis A.I., Papavassiliou A.G., Kyriazopoulou V.E., Sykiotis G.P., Habeos I.G.
ISSN
1939-327X (Electronic)
ISSN-L
0012-1797
Publication state
Published
Issued date
2011
Peer-reviewed
Oui
Volume
60
Number
10
Pages
2465-2473
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: ppublish
Abstract
OBJECTIVE: Obesity is characterized by chronic oxidative stress. Fibroblast growth factor 21 (FGF21) has recently been identified as a novel hormone that regulates metabolism. NFE2-related factor 2 (Nrf2) is a transcription factor that orchestrates the expression of a battery of antioxidant and detoxification genes under both basal and stress conditions. The current study investigated the role of Nrf2 in a mouse model of long-term high-fat diet (HFD)-induced obesity and characterized its crosstalk to FGF21 in this process.
RESEARCH DESIGN AND METHODS: Wild-type (WT) and Nrf2 knockout (Nrf2-KO) mice were fed an HFD for 180 days. During this period, food consumption and body weights were measured. Glucose metabolism was assessed by an intraperitoneal glucose tolerance test and intraperitoneal insulin tolerance test. Total RNA was prepared from liver and adipose tissue and was used for quantitative real-time RT-PCR. Fasting plasma was collected and analyzed for blood chemistries. The ST-2 cell line was used for transfection studies.
RESULTS: Nrf2-KO mice were partially protected from HFD-induced obesity and developed a less insulin-resistant phenotype. Importantly, Nrf2-KO mice had higher plasma FGF21 levels and higher FGF21 mRNA levels in liver and white adipose tissue than WT mice. Thus, the altered metabolic phenotype of Nrf2-KO mice under HFD was associated with higher expression and abundance of FGF21. Consistently, the overexpression of Nrf2 in ST-2 cells resulted in decreased FGF21 mRNA levels as well as in suppressed activity of a FGF21 promoter luciferase reporter.
CONCLUSIONS: The identification of Nrf2 as a novel regulator of FGF21 expands our understanding of the crosstalk between metabolism and stress defense.
Keywords
Animals, Dietary Fats/adverse effects, Fibroblast Growth Factors/genetics, Fibroblast Growth Factors/metabolism, Gene Expression Regulation/physiology, Genotype, Glucose Tolerance Test, Insulin Resistance, Liver/metabolism, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, NF-E2-Related Factor 2/genetics, NF-E2-Related Factor 2/metabolism, Obesity/etiology, Obesity/physiopathology, Promoter Regions, Genetic, RNA, Messenger/genetics, RNA, Messenger/metabolism
Pubmed
Web of science
Open Access
Yes
Create date
20/01/2015 14:40
Last modification date
20/08/2019 16:31
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