ArticleDiabetes2017
An Intestinal Farnesoid X Receptor-Ceramide Signaling Axis Modulates Hepatic Gluconeogenesis in Mice.
Article in Diabetes, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 116 papers, 1 of them a synthesis that pooled it.
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
116 citing papers in PubMed, 1 synthesis or guideline pooled it, 194 citations in OpenAlex.
- A systematic review on gut microbiota in type 2 diabetes mellitus.Frontiers in endocrinology · 2024Pooled it
- Saturated Fat Is More Metabolically Harmful for the Human Liver Than Unsaturated Fat or Simple Sugars.Diabetes care · 2018Trial
- Bile acids as a "new hormone" in aging-related liver disease.Life medicine · 2026Review
- Pulsatile FXR activation: Timing bile acid-targeted therapy to physiology.Acta pharmacologica Sinica · 2026Article
- Intestinal FXR deficiency uncouples steatosis protection from liver inflammation and fibrosis in MASH-diet fed mice.Scientific reports · 2026Article
- Dietary fat alters goblet cell function and microbial bile acid metabolism to promote intestinal lipid absorption in mice.Nature microbiology · 2026Article
- Detergents without a drain: the evolutionary logic (and liability) of sphingolipids.Journal of lipid research · 2026Review
- Disruption of bile acid homeostasis potentiates Paneth cell ablation by activating the intestinal Farnesoid X receptor in necrotizing enterocolitis.NPJ biofilms and microbiomes · 2026Article
- The bile acid-gut microbiota-vitamin D axis: new insights into biliary atresia.Frontiers in cellular and infection microbiology · 2026Review
- Xanthohumol and its non-estrogenic derivatives link to the gut-liver-brain axis to improve cognition in mice with diet-induced obesity.Frontiers in physiology · 2026Article
- Synergistic toxicity in alcohol-associated liver disease and PFAS exposure.Toxicological sciences : an official journal of the Society of Toxicology · 2025Review
- Review
- The Role of Five-Membered Aromatic Rings Containing N and O in Modulating Bile Acid Receptors: An Overview.ChemMedChem · 2025Review
- Ileal FXR Knockdown Ameliorates MASLD Progression in Rats via Modulating Bile Acid Metabolism Mediated by Gut Microbiota.Journal of gastroenterology and hepatology · 2025Article
- Ursodeoxycholic acid alleviates aortic aneurysm and dissection through the intestinal farnesoid X receptor/ceramide synthase 2 axis.Communications biology · 2025Article
- Novel Approaches in Glucose and Lipid Metabolism Disorder Therapy: Targeting the Gut Microbiota-Bile Acid Axis.Biology · 2025Review
- Pig bile powder maintains blood glucose homeostasis by promoting glucagon-like peptide-1 secretionWorld journal of diabetes · 2025Article
- Orchestration of Gut-Liver-Associated Transcription Factors in MAFLD: From Cross-Organ Interactions to Therapeutic Innovation.Biomedicines · 2025Review
- New drug therapies for metabolic dysfunction-associated steatohepatitis.Liver research (Beijing, China) · 2025Review
- Hepatic sphingomyelin phosphodiesterase 3 promotes steatohepatitis by disrupting membrane sphingolipid metabolism.Cell metabolism · 2025Article
56 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 6 institutions in 2 countries.
Funding
Abstract
Increasing evidence supports the view that intestinal farnesoid X receptor (FXR) is involved in glucose tolerance and that FXR signaling can be profoundly impacted by the gut microbiota. Selective manipulation of the gut microbiota-FXR signaling axis was reported to significantly impact glucose intolerance, but the precise molecular mechanism remains largely unknown. Here, caffeic acid phenethyl ester (CAPE), an over-the-counter dietary supplement and an inhibitor of bacterial bile salt hydrolase, increased levels of intestinal tauro-β-muricholic acid, which selectively suppresses intestinal FXR signaling. Intestinal FXR inhibition decreased ceramide levels by suppressing expression of genes involved in ceramide synthesis specifically in the intestinal ileum epithelial cells. The lower serum ceramides mediated decreased hepatic mitochondrial acetyl-CoA levels and pyruvate carboxylase (PC) activities and attenuated hepatic gluconeogenesis, independent of body weight change and hepatic insulin signaling in vivo; this was reversed by treatment of mice with ceramides or the FXR agonist GW4064. Ceramides substantially attenuated mitochondrial citrate synthase activities primarily through the induction of endoplasmic reticulum stress, which triggers increased hepatic mitochondrial acetyl-CoA levels and PC activities. These results reveal a mechanism by which the dietary supplement CAPE and intestinal FXR regulates hepatic gluconeogenesis and suggest that inhibiting intestinal FXR is a strategy for treating hyperglycemia.
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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.