ArticlePloS one2014
Hepatic farnesoid X-receptor isoforms α2 and α4 differentially modulate bile salt and lipoprotein metabolism in mice.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 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
16 citing papers in PubMed, 35 citations in OpenAlex.
- Microbiota-gut-brain axis and bile acids-driven neuromodulation.Neural regeneration research · 2026Article
- FXR Friend-ChIPs in the Enterohepatic System.Seminars in liver disease · 2023Review
- Role of FXR in Renal Physiology and Kidney Diseases.International journal of molecular sciences · 2023Review
- Molecular Basis of Bile Acid-FXR-FGF15/19 Signaling Axis.International journal of molecular sciences · 2022Review
- Review
- Role of Bile Acids and Nuclear Receptors in Acupuncture in Improving Crohn's Disease.Evidence-based complementary and alternative medicine : eCAM · 2022Review
- Bile Acids, Their Receptors, and the Gut Microbiota.Physiology (Bethesda, Md.) · 2021Review
- Farnesoid X receptor (FXR): Structures and ligands.Computational and structural biotechnology journal · 2021Review
- Farnesoid X receptor and bile acids regulate vitamin A storage.Scientific reports · 2019Article
- Male apoE*3-Leiden.CETP mice on high-fat high-cholesterol diet exhibit a biphasic dyslipidemic response, mimicking the changes in plasma lipids observed through life in men.Physiological reports · 2017Article
- Inhibition of ileal bile acid uptake protects against nonalcoholic fatty liver disease in high-fat diet-fed mice.Science translational medicine · 2016Article
- Novel role of a triglyceride-synthesizing enzyme: DGAT1 at the crossroad between triglyceride and cholesterol metabolism.Biochimica et biophysica acta · 2016Article
- Nuclear receptors and nonalcoholic fatty liver disease.Biochimica et biophysica acta · 2016Review
- Increased Bile Acid Synthesis and Impaired Bile Acid Transport in Human Obesity.The Journal of clinical endocrinology and metabolism · 2016Article
- Bioenergetic cues shift FXR splicing towards FXRα2 to modulate hepatic lipolysis and fatty acid metabolism.Molecular metabolism · 2015Article
- Bile acid nuclear receptor FXR and digestive system diseases.Acta pharmaceutica Sinica. B · 2015Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The nuclear receptor FXR acts as an intracellular bile salt sensor that regulates synthesis and transport of bile salts within their enterohepatic circulation. In addition, FXR is involved in control of a variety of crucial metabolic pathways. Four FXR splice variants are known, i.e. FXRα1-4. Although these isoforms show differences in spatial and temporal expression patterns as well as in transcriptional activity, the physiological relevance hereof has remained elusive. We have evaluated specific roles of hepatic FXRα2 and FXRα4 by stably expressing these isoforms using liver-specific self-complementary adeno-associated viral vectors in total body FXR knock-out mice. The hepatic gene expression profile of the FXR knock-out mice was largely normalized by both isoforms. Yet, differential effects were also apparent; FXRα2 was more effective in reducing elevated HDL levels and transrepressed hepatic expression of Cyp8b1, the regulator of cholate synthesis. The latter coincided with a switch in hydrophobicity of the bile salt pool. Furthermore, FXRα2-transduction caused an increased neutral sterol excretion compared to FXRα4 without affecting intestinal cholesterol absorption. Our data show, for the first time, that hepatic FXRα2 and FXRα4 differentially modulate bile salt and lipoprotein metabolism in mice.
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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.