Evidence map›Paper›PMID 25617503›Full record

Trial reportJournal of hepatology2015

Ursodeoxycholic acid exerts farnesoid X receptor-antagonistic effects on bile acid and lipid metabolism in morbid obesity.

Michaela Mueller, Anders Thorell, Thierry Claudel, Pooja Jha, Harald Koefeler, Carolin Lackner, Bastian Hoesel, Guenter Fauler, Tatjana Stojakovic, Curt Einarsson and 2 more

Open access · hybridAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Journal of hepatology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 166 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
166citing papers in PubMed, 1 pooled it
13.7field-weighted citation impact, top 1% 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

166 citing papers in PubMed, 1 synthesis or guideline pooled it, 301 citations in OpenAlex.

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  9. Ursodeoxycholic acid: Effects on hepatic unfolded protein response, apoptosis and oxidative stress in morbidly obese patients.Liver international : official journal of the International Association for the Study of the Liver · 2018
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106 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 4 institutions in 2 countries.

Michaela MuellerHans Popper Laboratory of Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Laboratory of Experimental and Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Medicine, Medical University of Graz, Graz, Austria.
Anders ThorellKarolinska Institutet, Department of Clinical Science at Danderyds Hospital, Stockholm, Sweden; Department of Surgery, Ersta Hospital, Stockholm, Sweden.
Thierry ClaudelHans Popper Laboratory of Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
Pooja JhaHans Popper Laboratory of Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; Laboratory of Experimental and Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Medicine, Medical University of Graz, Graz, Austria.
Harald KoefelerCore Facility for Mass Spectrometry, Medical University of Graz, Graz, Austria.
Carolin LacknerInstitute of Pathology, Medical University of Graz, Graz, Austria.
Bastian HoeselDepartment of Vascular Biology and Thrombosis Research, Center for Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria.
Guenter FaulerClinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.
Tatjana StojakovicClinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.
Curt EinarssonKarolinska Institutet, Department of Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden.
Hanns-Ulrich MarschallInstitute of Medicine, Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden. Electronic address: hanns-ulrich.marschall@gu.se.
Michael TraunerHans Popper Laboratory of Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria. Electronic address: michael.trauner@meduniwien.ac.at.
Medical University of Vienna · ATMedical University of Graz · ATKarolinska Institutet · SEUniversity of Gothenburg · SE

Funding

Austrian Science Fund FWF F 3008Austrian Science Fund FWF W 1226
6 · The paper itself

Abstract

BACKGROUND &

aimsBile acids (BAs) are major regulators of hepatic BA and lipid metabolism but their mechanisms of action in non-alcoholic fatty liver disease (NAFLD) are still poorly understood. Here we aimed to explore the molecular and biochemical mechanisms of ursodeoxycholic acid (UDCA) in modulating the cross-talk between liver and visceral white adipose tissue (vWAT) regarding BA and cholesterol metabolism and fatty acid/lipid partitioning in morbidly obese NAFLD patients.

methodsIn this randomized controlled pharmacodynamic study, we analyzed serum, liver and vWAT samples from 40 well-matched morbidly obese patients receiving UDCA (20 mg/kg/day) or no treatment three weeks prior to bariatric surgery.

resultsShort term UDCA administration stimulated BA synthesis by reducing circulating fibroblast growth factor 19 and farnesoid X receptor (FXR) activation, resulting in cholesterol 7α-hydroxylase induction mirrored by elevated C4 and 7α-hydroxycholesterol. Enhanced BA formation depleted hepatic and LDL-cholesterol with subsequent activation of the key enzyme of cholesterol synthesis 3-hydroxy-3-methylglutaryl-CoA reductase. Blunted FXR anti-lipogenic effects induced lipogenic stearoyl-CoA desaturase (SCD) in the liver, thereby increasing hepatic triglyceride content. In addition, induced SCD activity in vWAT shifted vWAT lipid metabolism towards generation of less toxic and more lipogenic monounsaturated fatty acids such as oleic acid.

conclusionThese data demonstrate that by exerting FXR-antagonistic effects, UDCA treatment in NAFLD patients strongly impacts on cholesterol and BA synthesis and induces neutral lipid accumulation in both liver and vWAT.

Indexed as

Bile Acids and SaltsHumansIntra-Abdominal FatLipid MetabolismLiverNon-alcoholic Fatty Liver DiseaseObesity, MorbidOleic AcidReceptor, Farnesoid X-ActivatedReceptors, Cytoplasmic and NuclearStearoyl-CoA DesaturaseUrsodeoxycholic AcidBile Acids and SaltsOleic AcidReceptor, Farnesoid X-ActivatedReceptors, Cytoplasmic and NuclearSCD1 protein, humanStearoyl-CoA DesaturaseUrsodeoxycholic Acid3-hydroxy-3-methylglutaryl-CoA reductaseFGF19LipogenesisNon-alcoholic fatty liver diseaseStearoyl-CoA desaturase

Identifiers

PMID25617503
PMCPMC4451470
OpenAlexW2063009130

What OpenQuestion holds

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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.