ArticleThe Journal of biological chemistry2009
FGF15/FGFR4 integrates growth factor signaling with hepatic bile acid metabolism and insulin action.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 112 citations in OpenAlex.
- Serum Fibroblast Growth Factor 19 and Total Bile Acid Concentrations Are Potential Biomarkers of Hepatocellular Carcinoma in Patients with Type 2 Diabetes Mellitus.BioMed research international · 2020Trial
- The role of FGF19-FGFR4 signaling pathway in liver health and disease: Guardian or destroyer.Genes & diseases · 2026Review
- Bile acid signaling in health and disease.Molecular biomedicine · 2026Review
- FGF family in health and disease.Molecular biomedicine · 2026Review
- Alterations in intestinal bile acid transport provide a therapeutic target in patients with post-bariatric hypoglycaemia.Nature metabolism · 2025Article
- Branched-chain amino acids promote hepatic Cyp7a1 expression and bile acid synthesis via suppressing FGF21-ERK pathway.Acta pharmacologica Sinica · 2025Article
- Article
- Pathogenetic therapeutic approaches for endocrine diseases based on antisense oligonucleotides and RNA-interference.Frontiers in endocrinology · 2025Review
- Engineered FGF19BMC biotechnology · 2023Article
- Fibroblast growth factor 15, induced by elevated bile acids, mediates the improvement of hepatic glucose metabolism after sleeve gastrectomy.World journal of gastroenterology · 2023Article
- Proteogenomic links to human metabolic diseases.Nature metabolism · 2023Article
- Vitamin D-VDR Novel Anti-Inflammatory Molecules-New Insights into Their Effects on Liver Diseases.International journal of molecular sciences · 2022Review
- Dietary Exposure to Antibiotic Residues Facilitates Metabolic Disorder by Altering the Gut Microbiota and Bile Acid Composition.mSystems · 2022Article
- TCF7L2 transcriptionally regulates Fgf15 to maintain bile acid and lipid homeostasis through gut-liver crosstalk.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Intestinal farnesoid X receptor signaling controls hepatic fatty acid oxidation.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2022Article
- Dietary acetic acid suppress high-fat diet-induced obesity in mice by altering taurine conjugated bile acids metabolism.Current research in food science · 2022Article
- Cholesterol-lowering effects of taurine through the reduction of ileal FXR signaling due to the alteration of ileal bile acid composition.Amino acids · 2021Article
- Hepatic metabolic regulation by nuclear factor E4BP4.Journal of molecular endocrinology · 2021Review
- The Role of FGF19 and MALRD1 in Enterohepatic Bile Acid Signaling.Frontiers in endocrinology · 2021Review
- AInternational journal of molecular sciences · 2020Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The current studies show FGF15 signaling decreases hepatic forkhead transcription factor 1 (FoxO1) activity through phosphatidylinositol (PI) 3-kinase-dependent phosphorylation. The bile acid receptor FXR (farnesoid X receptor) activates expression of fibroblast growth factor (FGF) 15 in the intestine, which acts through hepatic FGFR4 to suppress cholesterol-7alpha hydroxylase (CYP7A1) and limit bile acid production. Because FoxO1 activity and CYP7A1 gene expression are both increased by fasting, we hypothesized CYP7A1 might be a FoxO1 target gene. Consistent with recently reported results, we show CYP7A1 is a direct target of FoxO1. Additionally, we show that the PI 3-kinase pathway is key for both the induction of CYP7A1 by fasting and the suppression by FGF15. FGFR4 is the major hepatic FGF receptor isoform and is responsible for the hepatic effects of FGF15. We also show that expression of FGFR4 in liver was decreased by fasting, increased by insulin, and reduced by streptozotocin-induced diabetes, implicating FGFR4 as a primary target of insulin regulation. Because insulin and FGF both target the PI 3-kinase pathway, these observations suggest FoxO1 is a key node in the convergence of FGF and insulin signaling pathways and functions as a key integrator for the regulation of glucose and bile acid metabolism.
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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.