ArticleLiver international : official journal of the International Association for the Study of the Liver2015
Protective effects of farnesoid X receptor (FXR) on hepatic lipid accumulation are mediated by hepatic FXR and independent of intestinal FGF15 signal.
Article in Liver international : official journal of the International Association for the Study of the Liver, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 132 citations in OpenAlex.
- Disulfiram ameliorates nonalcoholic steatohepatitis by modulating the gut microbiota and bile acid metabolism.Nature communications · 2022Trial
- The Farnesoid X receptor-bile acid axis contributes to immune evasion in gastric cancer and its inhibition enhances efficacy of anti-PD-L1 therapy.Biochemistry and biophysics reports · 2026Article
- Ileal FXR Knockdown Ameliorates MASLD Progression in Rats via Modulating Bile Acid Metabolism Mediated by Gut Microbiota.Journal of gastroenterology and hepatology · 2025Article
- Liver-specific Nr1h4 deletion in mice with human-like bile acid composition causes severe liver injury.Journal of lipid research · 2025Article
- Caffeic acid and chlorogenic acid mediate the ADPN-AMPK-PPARα pathway to improve fatty liver and production performance in laying hens.Journal of animal science and biotechnology · 2025Article
- Analyzing MASLD interventional clinical trial registration based on the ClinicalTrials.gov database.BMC gastroenterology · 2025Article
- Reversing metabolic dysregulation in farnesoid X receptor knockout mice via gut microbiota modulation.PloS one · 2025Article
- Molecular targets of PXR-dependent ethanol-induced hepatotoxicity in female mice.Biochemical pharmacology · 2024Article
- Impact of Plant-Based Dietary Fibers on Metabolic Homeostasis in High-Fat Diet Mice via Alterations in the Gut Microbiota and Metabolites.The Journal of nutrition · 2024Article
- Bile acid metabolism and signaling in health and disease: molecular mechanisms and therapeutic targets.Signal transduction and targeted therapy · 2024Review
- Proanthocyanidins-Based Synbiotics as a Novel Strategy for Nonalcoholic Fatty Liver Disease (NAFLD) Risk Reduction.Molecules (Basel, Switzerland) · 2024Review
- Review
- Chitobiose exhibited a lipid-lowering effect in ob/obBioresources and bioprocessing · 2023Article
- RISING STARS: Endocrine regulation of metabolic homeostasis via the intestine and gut microbiome.The Journal of endocrinology · 2023Review
- Current, emerging, and potential therapies for non-alcoholic steatohepatitis.Frontiers in pharmacology · 2023Review
- Article
- Farnesoid X receptor regulates PIFish physiology and biochemistry · 2022Article
- Effects of Dietary Inclusion of β-Hydroxy-β-Methylbutyrate on Growth Performance, Fat Deposition, Bile Acid Metabolism, and Gut Microbiota Function in High-Fat and High-Cholesterol Diet-Challenged Layer Chickens.Current issues in molecular biology · 2022Article
- Farnesoid X receptor (FXR) agonists induce hepatocellular apoptosis and impair hepatic functions via FXR/SHP pathway.Archives of toxicology · 2022Article
- Molecular interactions between the intestinal microbiota and the host.Molecular microbiology · 2022Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
Abstract
BACKGROUND &
aimsThere is a growing evidence that bile acids are involved in the regulation of triglyceride-, cholesterol-homoeostasis and fat absorption. In this study organ-specific Fxr knockout mice were used to further investigate the influence of farnesoid X receptor FXR in lipogenesis.
methodsLiver- and intestine-specific Fxr knockout mice were fed a 1% cholesterol diet for 28 days. Histological examination of frozen tissue sections included Sudan III/H&E, BODIPY staining and liver X receptor (LXR) immunohistochemistry. Liver triglycerides, serum cholesterol, serum bile acids and nuclear LXR protein were measured. mRNA expression of several genes involved in bile acid-, cholesterol-homoeostasis and lipogenesis was quantified by real-time PCR.
resultsHepatic FXR deficiency contributes to lipid accumulation under 1% cholesterol administration which is not observed in intestinal Fxr knockout mice. Strong lipid accumulation, characterized by larger vacuoles could be observed in hepatic Fxr knockout sections, while intestinal Fxr knockout mice show no histological difference to controls. In addition, these mice have the ability to maintain normal serum cholesterol and bile acid levels. Hepatic Fxr knockouts were characterized by elevated triglycerides and bile acid levels. Expression level of LXR was significantly elevated under control and 1% cholesterol diet in hepatic Fxr knockout mice and was followed by concomitant lipogenic target gene induction such as Fas and Scd-1. This protective FXR effect against hepatic lipid accumulation was independent of intestinal Fgf15 induction.
conclusionThese results show that the principal site of protective bile acid signalling against lipid accumulation is located in the liver since the absence of hepatic but not intestinal FXR contributes to lipid accumulation under cholesterol diet.
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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.