Evidence map›Paper›PMID 25156247›Full record

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.

Johannes Schmitt, Bo Kong, Bruno Stieger, Oliver Tschopp, Simon M Schultze, Monika Rau, Achim Weber, Beat Müllhaupt, Grace L Guo, Andreas Geier

Open access · greenAbstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
58citing papers in PubMed
3.7field-weighted citation impact, top 5% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

58 citing papers in PubMed, 132 citations in OpenAlex.

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  13. Chitobiose exhibited a lipid-lowering effect in ob/obBioresources and bioprocessing · 2023
    Article
  14. Review
  15. Review
  16. Article
  17. Farnesoid X receptor regulates PIFish physiology and biochemistry · 2022
    Article
  18. Article
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  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 3 countries.

Johannes Schmitt *Division of Hepatology, Department of Medicine II, University Hospital Wuerzburg, DE-97080 Wuerzburg, Germany.
Bo Kong *Department of Pharmacology and Toxicology Ernest Mario School of Pharmacy Rutgers University Piscataway, NJ 08854, USA.
Bruno StiegerDepartment of Clinical Pharmacology and Toxicology, University Hospital Zurich (USZ), CH-8091 Zurich, Switzerland.
Oliver TschoppDivision of Endocrinology, Diabetes, & Nutrition, University Hospital of Zurich, Zurich, Switzerland.
Simon M SchultzeDivision of Endocrinology, Diabetes, & Nutrition, University Hospital of Zurich, Zurich, Switzerland.
Monika RauDivision of Hepatology, Department of Medicine II, University Hospital Wuerzburg, DE-97080 Wuerzburg, Germany.
Achim WeberDepartment of Pathology, Institute of Surgical Pathology, University Hospital Zurich (USZ), Zurich, Switzerland.
Beat MüllhauptDepartment of Gastroenterology & Hepatology, University Hospital Zurich (USZ), Zurich, Switzerland.
Grace L Guo *Department of Pharmacology and Toxicology Ernest Mario School of Pharmacy Rutgers University Piscataway, NJ 08854, USA.
Andreas Geier *Division of Hepatology, Department of Medicine II, University Hospital Wuerzburg, DE-97080 Wuerzburg, Germany.
University Hospital of Zurich · CHRutgers, The State University of New Jersey · USUniversitätsklinikum Würzburg · DE

Funding

Translational Research Support CoreP30ES005022 · NIEHS · UNIV OF MED/DENT NJ-R W JOHNSON MED SCH · PI ROBERT John LAUMBACH · 1988 to 2026
$47.4M
THE ROLE OF HUMAN PXR IN ANTI-TUBERCULOSIS DRUG-INDUCED LIVER INJURYP20RR021940 · NCRR · UNIVERSITY OF KANSAS MEDICAL CENTER · PI COPPLE, BRYAN L · 2006 to 2011
$12.1M
Nuclear Receptors in Liver Health and DiseaseP20GM103549 · NIGMS · UNIVERSITY OF KANSAS MEDICAL CENTER · PI JAESCHKE, HARTMUT W. · 2012 to 2015
$8.1M
Tissue specific mechanism of FXR in suppressing bile-acid synthesisR01DK081343 · NIDDK · UNIVERSITY OF KANSAS MEDICAL CENTER · PI GUO, GRACE L · 2008 to 2011
$1.3M
Gut bile acids, Fxr, & Fgf15 in total parenteral nutrition-associated cholestasisR01GM104037 · NIGMS · RUTGERS, THE STATE UNIV OF N.J. · PI GUO, GRACE L · 2013 to 2016
$1.1M
FXR, nuclear receptors, and transcriptional regulation of liver homeostasisR56DK090036 · NIDDK · UNIVERSITY OF KANSAS MEDICAL CENTER · PI GUO, GRACE L · 2011 to 2011
$328k
NCRR NIH HHS P20 RR021940NCRR NIH HHS P20-RR021940NIDDK NIH HHS DK031343-01NIDDK NIH HHS R01 DK081343NIDDK NIH HHS R56 DK090036NIEHS NIH HHS P30 ES005022NIGMS NIH HHS P20 GM103549NIGMS NIH HHS R01 GM104037
6 · The paper itself

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.

Indexed as

Signal TransductionAnimalsBile Acids and SaltsCholesterol, DietaryDisease Models, Animalfas ReceptorFibroblast Growth FactorsGene Expression RegulationIntestinal MucosaLiverLiver X ReceptorsMaleMice, Inbred C57BLMice, KnockoutNon-alcoholic Fatty Liver DiseaseOrphan Nuclear ReceptorsBile Acids and SaltsCholesterol, DietaryFas protein, mousefas Receptorfibroblast growth factor 15, mouseFibroblast Growth FactorsLiver X ReceptorsOrphan Nuclear ReceptorsReceptor, Farnesoid X-ActivatedReceptors, Cytoplasmic and NuclearScd1 protein, mouseStearoyl-CoA DesaturaseTriglyceridesbile acidsFXRlipogenesisNAFLD

Identifiers

PMID25156247
PMCPMC4146754
OpenAlexW2075331768

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Registered trials

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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.