ArticleMolecular metabolism2015
Bioenergetic cues shift FXR splicing towards FXRα2 to modulate hepatic lipolysis and fatty acid metabolism.
Article in Molecular metabolism, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed, 45 citations in OpenAlex.
- Serine Starvation Modulates mRNA Splicing through Translational Inhibition of SRSF Proteins.Cancer research · 2026Article
- Exercise-Induced Changes in Enterohepatic Communication Are Linked to Liver Steatosis Resolution.Nutrients · 2025Article
- IGFBP1 orchestrates metabolic reprogramming to drive clear cell renal cell carcinoma progression through NR1H4-mediated lipid homeostasis disruption.Cancer cell international · 2025Article
- Farnesoid X receptor‑driven metabolic plasticity: Bridging physiological adaptation and malignant transformation in lipid handling (Review).International journal of molecular medicine · 2025Review
- The farnesoid X receptor activates transcription independently of RXR at non-canonical response elements.Nucleic acids research · 2025Article
- Alternative splicing: hallmark and therapeutic opportunity in metabolic liver disease.Gastroenterology report · 2025Review
- Alternative splicing is an FXRα loss-of-function mechanism and impacts energy metabolism in hepatocarcinoma cells.The Journal of biological chemistry · 2025Article
- Review
- The role of botanical triterpenoids and steroids in bile acid metabolism, transport, and signaling: Pharmacological and toxicological implications.Acta pharmaceutica Sinica. B · 2024Review
- The Farnesoid X Receptor as a Master Regulator of Hepatotoxicity.International journal of molecular sciences · 2022Review
- Enterohepatic and non-canonical roles of farnesoid X receptor in controlling lipid and glucose metabolism.Molecular and cellular endocrinology · 2022Review
- Molecular Basis of Bile Acid-FXR-FGF15/19 Signaling Axis.International journal of molecular sciences · 2022Review
- Improving human mesenchymal stem cell-derived hepatic cell energy metabolism by manipulating glucose homeostasis and glucocorticoid signaling.Frontiers in endocrinology · 2022Article
- FXR, a Key Regulator of Lipid Metabolism, Is Inhibited by ER Stress-Mediated Activation of JNK and p38 MAPK in Large Yellow Croakers (Nutrients · 2021Article
- Bile Acids, Their Receptors, and the Gut Microbiota.Physiology (Bethesda, Md.) · 2021Review
- RNA Splicing: A Versatile Regulatory Mechanism in Pediatric Liver Diseases.Frontiers in molecular biosciences · 2021Review
- Combined Analysis of Expression Profiles in a Mouse Model and Patients Identified BHMT2 as a New Regulator of Lipid Metabolism in Metabolic-Associated Fatty Liver Disease.Frontiers in cell and developmental biology · 2021Article
- AInternational journal of molecular sciences · 2020Article
- Bile acids mediated potential functional interaction between FXR and FATP5 in the regulation of Lipid Metabolism.International journal of biological sciences · 2020Review
- Farnesoid X receptor and bile acids regulate vitamin A storage.Scientific reports · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 4 institutions in 4 countries.
Funding
Abstract
objectiveFarnesoid X receptor (FXR) plays a prominent role in hepatic lipid metabolism. The FXR gene encodes four proteins with structural differences suggestive of discrete biological functions about which little is known.
methodsWe expressed each FXR variant in primary hepatocytes and evaluated global gene expression, lipid profile, and metabolic fluxes. Gene delivery of FXR variants to Fxr(-/-) mouse liver was performed to evaluate their role in vivo. The effects of fasting and physical exercise on hepatic Fxr splicing were determined.
resultsWe show that FXR splice isoforms regulate largely different gene sets and have specific effects on hepatic metabolism. FXRα2 (but not α1) activates a broad transcriptional program in hepatocytes conducive to lipolysis, fatty acid oxidation, and ketogenesis. Consequently, FXRα2 decreases cellular lipid accumulation and improves cellular insulin signaling to AKT. FXRα2 expression in Fxr(-/-) mouse liver activates a similar gene program and robustly decreases hepatic triglyceride levels. On the other hand, FXRα1 reduces hepatic triglyceride content to a lesser extent and does so through regulation of lipogenic gene expression. Bioenergetic cues, such as fasting and exercise, dynamically regulate Fxr splicing in mouse liver to increase Fxrα2 expression.
conclusionsOur results show that the main FXR variants in human liver (α1 and α2) reduce hepatic lipid accumulation through distinct mechanisms and to different degrees. Taking this novel mechanism into account could greatly improve the pharmacological targeting and therapeutic efficacy of FXR agonists.
Indexed as
Identifiers
What OpenQuestion holds
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.