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Glucose induces FGF21 mRNA expression through ChREBP activation in rat hepatocytes
Open accessAbstract
Fibroblast growth factor 21 (FGF21) has beneficial effects of improving the plasma glucose and lipid profiles in diabetic rodents. Here, we investigated carbohydrate response element binding protein (ChREBP) involvement in the regulation of FGF21 mRNA expression in liver. Glucose stimulation and adenoviral overexpression of dominant active ChREBP increased FGF21 mRNA. Consistently, adenoviral expression of dominant negative Mlx inhibited glucose induction of FGF21 mRNA. Furthermore, deletion studies of mouse FGF21 gene promoter (−2000 to +65 bp) revealed a glucose responsive region between −74 and −52 bp. These findings suggest that FGF21 expression is regulated by ChREBP.
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In the citing paper
“Hepatic mRNA and plasma protein levels of FGF21 are induced by high sugar intake through a mechanism dependent on the transcription factor ChREBP22–25”
From Metabolic messengers: FGF21 (2021) · cites this paper as [23]
In the citing paper
“An intermediate in this pathway, xylulose-5-phosphate, activates ChREBP (1) and promotes its binding to the carbohydrate response element sites in the promoters of target genes, including FGF21 (53, 130).”
From Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis (2018) · cites this paper as [53]
In the citing paper
“The stimulation of FGF21 production by carbohydrates is mediated by the transcription factor carbohydrate-response element-binding protein (ChREBP).”
From Fibroblast Growth Factor 21: A Versatile Regulator of Metabolic Homeostasis (2018) · cites this paper as [53]
In the citing paper
“Circulating FGF21 levels are robustly increased by diets that are high in carbohydrate but low in protein”
From FGF21 and the physiological regulation of macronutrient preference (2020) · cites this paper as [137]
In the citing paper
“liver FGF21 production seems to be robustly stimulated by an imbalance in macronutrients, particularly settings of high-carbohydrate but low-protein intake”
From FGF21 and the physiological regulation of macronutrient preference (2020) · cites this paper as [137]
In the citing paper
“Both acute carbohydrate ingestion and long-term exposure to high-carbohydrate diets significantly increase liver FGF21 mRNA expression and circulating FGF21 levels”
From FGF21 and the physiological regulation of macronutrient preference (2020) · cites this paper as [137]
In the citing paper
“driven at least in part by the transcription factor carbohydrate response element binding protein (ChREBP), which binds directly to the FGF21 promoter”
From FGF21 and the physiological regulation of macronutrient preference (2020) · cites this paper as [137]
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Citations
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Metadata
- Authors
- Iizuka, K., Takeda, J., & Horikawa, Y.
- Affiliations
- Gunma University (JP)
- Gifu University (JP)
- Corresponding author
- Horikawa, Yukio
- Venue
- FEBS Letters
- Publisher
- Wiley
- Published
- 2009-08-04
- Volume
- 583
- Issue
- 17
- Pages
- 2882-2886
- ISSN
- 0014-5793 (ISSN-L)
- 1873-3468
- OpenAlex
- W2075349430
- Cited by
- 187
- References
- 25
- Citations by year
- 2026: 5 · 2025: 12 · 2024: 6 · 2023: 9 · 2022: 15 · 2021: 22 · 2020: 8 · 2019: 16 · 2018: 12 · 2017: 18 · 2016: 20 · 2015: 13 · 2014: 7 · 2013: 6 · 2012: 10
- FWCI
- 2.55
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- FEBS Letters (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science
- New Energy and Industrial Technology Development Organization
- Health and Labor Science Research Grant for Research on Human Genome
- Japanese Ministry of Health, Labor and Welfare
- ONO Medical Research Foundation
- Kao Research Council for the Study of Healthcare Science
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- FGF21, ChREBP, glucose, hepatocytes, MLX, transcriptional regulation
- MeSH terms
- Animals, Cells, Cultured, Fibroblast Growth Factors, Glucose, Promoter Regions, Genetic, RNA, Messenger, Transcriptional Activation, Trans-Activators, Hepatocytes, Mice, Rats, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
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