ArticleThe Journal of clinical investigation2021
Suppressing the intestinal farnesoid X receptor/sphingomyelin phosphodiesterase 3 axis decreases atherosclerosis.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers, 1 of them a synthesis that pooled it.
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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
72 citing papers in PubMed, 1 synthesis or guideline pooled it, 123 citations in OpenAlex.
- Macrophage Subsets and Death Are Responsible for Atherosclerotic Plaque Formation.Frontiers in immunology · 2022Pooled it
- Modulation of the Serum Metabolome by the Short-Chain Fatty Acid Propionate: Potential Implications for Its Cholesterol-Lowering Effect.Nutrients · 2024Trial
- Bile acid signaling in health and disease.Molecular biomedicine · 2026Review
- Discovery of sulfonyl benzoic acid derivatives with joint TGR5-agonist and FXR-antagonist activity for myocardial ischemia/reperfusion injury protection.Acta pharmaceutica Sinica. B · 2026Article
- Causal Effects of Hydrophilic Bile Acids on Carfilzomib-Related Cardiovascular Events in Multiple Myeloma: A Mendelian Randomization Study.Clinical pharmacology and therapeutics · 2026Article
- 4-Hydroxyphenanthrene exacerbates obesity by altering gut microbiota and bile acid metabolism.Nature communications · 2026Article
- Rosemary-derived triterpene acids improve growth and lipid metabolism in juvenile grass carp (Ctenopharyngodon idella) through the gut-liver axis by tissue-specifically regulating the farnesoid X receptor.Journal of animal science and biotechnology · 2026Article
- Bile acid signaling: from dynamic pool composition to inter-organ communication.Frontiers in endocrinology · 2026Review
- Emerging insights of bile acids in cardiovascular physiology and disease: from molecular mechanisms to therapeutic potential.Frontiers in pharmacology · 2026Review
- The gut microbiota-bile acid-FXR axis in NAFLD: from progression to therapeutic applications.Frontiers in physiology · 2026Review
- The Impact of Gut Microbial Metabolomics on Type 2 Diabetes Development in People Living with HIV.Metabolites · 2025Review
- Hepatic Mechanisms of Myocardial Infarction: A New Perspective in Metabolic Dysfunction-Associated Fatty Liver Disease.Journal of the American Heart Association · 2025Review
- Advances of exosome regulating‑FXR to repair inflammatory bowel disease (Review).International journal of molecular medicine · 2025Review
- Cholecystectomy-related gut microbiota dysbiosis exacerbates colorectal tumorigenesis.Nature communications · 2025Article
- Differential roles of individual bile acid in physiology and disease.Pharmacological research · 2025Review
- Nuclear receptors in health and disease: signaling pathways, biological functions and pharmaceutical interventions.Signal transduction and targeted therapy · 2025Review
- Ursodeoxycholic acid alleviates aortic aneurysm and dissection through the intestinal farnesoid X receptor/ceramide synthase 2 axis.Communications biology · 2025Article
- Discovery of metabolic biomarkers for distinguishing LAA and SVO subtypes of acute ischemic stroke.Scientific reports · 2025Article
- Farnesoid X receptor‑driven metabolic plasticity: Bridging physiological adaptation and malignant transformation in lipid handling (Review).International journal of molecular medicine · 2025Review
- A critical role forActa pharmaceutica Sinica. B · 2025Article
12 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 3 institutions in 2 countries.
Funding
Abstract
Intestinal farnesoid X receptor (FXR) signaling is involved in the development of obesity, fatty liver disease, and type 2 diabetes. However, the role of intestinal FXR in atherosclerosis and its potential as a target for clinical treatment have not been explored. The serum levels of fibroblast growth factor 19 (FGF19), which is encoded by an FXR target gene, were much higher in patients with hypercholesterolemia than in control subjects and were positively related to circulating ceramide levels, indicating a link between intestinal FXR, ceramide metabolism, and atherosclerosis. Among ApoE-/- mice fed a high-cholesterol diet (HCD), intestinal FXR deficiency (in FxrΔIE ApoE-/- mice) or direct FXR inhibition (via treatment with the FXR antagonist glycoursodeoxycholic acid [GUDCA]) decreased atherosclerosis and reduced the levels of circulating ceramides and cholesterol. Sphingomyelin phosphodiesterase 3 (SMPD3), which is involved in ceramide synthesis in the intestine, was identified as an FXR target gene. SMPD3 overexpression or C16:0 ceramide supplementation eliminated the improvements in atherosclerosis in FxrΔIE ApoE-/- mice. Administration of GUDCA or GW4869, an SMPD3 inhibitor, elicited therapeutic effects on established atherosclerosis in ApoE-/- mice by decreasing circulating ceramide levels. This study identified an intestinal FXR/SMPD3 axis that is a potential target for atherosclerosis therapy.
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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.