ArticleThe Journal of biological chemistry2010
Transcriptional repressor E4-binding protein 4 (E4BP4) regulates metabolic hormone fibroblast growth factor 21 (FGF21) during circadian cycles and feeding.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
66 citing papers in PubMed, 105 citations in OpenAlex.
- Mutually exclusive alternative pre-mRNA splicing promotes adaptive metabolic stress signaling by JNK.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Maternal food-derived signals oscillate in the fetal suprachiasmatic nucleus before its circadian clock develops.PLoS biology · 2025Article
- Feeding regime synchronizes circadian clock in choroid plexus - insight into a complex mechanism.Cellular and molecular life sciences : CMLS · 2025Article
- Circadian clock communication during homeostasis and ageing.Nature reviews. Molecular cell biology · 2025Review
- The time is now: accounting for time-of-day effects to improve reproducibility and translation of metabolism research.Nature metabolism · 2025Review
- Deletion of Arntl, a component of the molecular clock, in adipocytes leads to cellular hypertrophy by increasing insulin sensitivity via FGF21.Npj biological timing and sleep · 2025Article
- OPN-Mediated Crosstalk Between Hepatocyte E4BP4 and Hepatic Stellate Cells Promotes MASH-Associated Liver Fibrosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Circadian patterns of growth factor receptor-dependent signaling and implications for carcinogenesis.Cell communication and signaling : CCS · 2024Review
- Circadian Regulation of Endocrine Fibroblast Growth Factors on Systemic Energy Metabolism.Molecular pharmacology · 2024Review
- Review
- A pan-cancer characterization of immune-related NFIL3 identifies potential predictive biomarker.Journal of Cancer · 2024Article
- Novel Roles for the Transcriptional Repressor E4BP4 in Both Cardiac Physiology and Pathophysiology.JACC. Basic to translational science · 2023Article
- A new border for circadian rhythm gene NFIL3 in diverse fields of cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023Review
- The biological clock enhancer nobiletin ameliorates steatosis in genetically obese mice by restoring aberrant hepatic circadian rhythm.American journal of physiology. Gastrointestinal and liver physiology · 2022Article
- Establishment of H3K9-methylated heterochromatin and its functions in tissue differentiation and maintenance.Nature reviews. Molecular cell biology · 2022Review
- Article
- Fibroblast Growth Factor 21 Facilitates the Homeostatic Control of Feeding Behavior.Journal of clinical medicine · 2022Review
- Hepatic FGF21: Its Emerging Role in Inter-Organ Crosstalk and Cancers.International journal of biological sciences · 2022Review
- New insight into ischemic stroke: Circadian rhythm in post-stroke angiogenesis.Frontiers in pharmacology · 2022Review
- Circadian Clock and Liver Cancer.Cancers · 2021Review
6 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Fibroblast growth factor 21 (FGF21) is a potent antidiabetic and triglyceride-lowering hormone whose hepatic expression is highly responsive to food intake. FGF21 induction in the adaptive response to fasting has been well studied, but the molecular mechanism responsible for feeding-induced repression remains unknown. In this study, we demonstrate a novel link between FGF21 and a key circadian output protein, E4BP4. Expression of Fgf21 displays a circadian rhythm, which peaks during the fasting phase and is anti-phase to E4bp4, which is elevated during feeding periods. E4BP4 strongly suppresses Fgf21 transcription by binding to a D-box element in the distal promoter region. Depletion of E4BP4 in synchronized Hepa1c1c-7 liver cells augments the amplitude of Fgf21 expression, and overexpression of E4BP4 represses FGF21 secretion from primary mouse hepatocytes. Mimicking feeding effects, insulin significantly increases E4BP4 expression and binding to the Fgf21 promoter through AKT activation. Thus, E4BP4 is a novel insulin-responsive repressor of FGF21 expression during circadian cycles and feeding.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.