Evidence mapPaperPMID 39608059Full record

ArticleEBioMedicine2024

FGF21 and its underlying adipose tissue-liver axis inform cardiometabolic burden and improvement in obesity after metabolic surgery.

Marie Patt, Isabel Karkossa, Laura Krieg, Lucas Massier, Kassem Makki, Shirin Tabei, Thomas Karlas, Arne Dietrich, Martin Gericke, Michael Stumvoll and 5 more

Abstract read
In one paragraph

Article in EBioMedicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
field-weighted citation impact
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

6 citing papers in PubMed.

  1. Review
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  3. Article
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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

15 authors.

Marie PattUniversity of Leipzig Medical Centre, Medical Department III-Endocrinology, Nephrology, Rheumatology, Leipzig, Germany.
Isabel KarkossaDepartment of Molecular Systems Biology, Helmholtz-Centre for Environmental Research - UFZ, Leipzig, Germany.
Laura KriegDepartment of Molecular Systems Biology, Helmholtz-Centre for Environmental Research - UFZ, Leipzig, Germany.
Lucas MassierUniversity of Leipzig Medical Centre, Medical Department III-Endocrinology, Nephrology, Rheumatology, Leipzig, Germany; Department of Medicine (H7), Karolinska Institutet, Stockholm, Sweden.
Kassem MakkiINSERM U1060, INRAE UMR1397, Université de Lyon, France.
Shirin TabeiInstitute of Endocrinology and Diabetes, University of Lübeck, Lübeck, Germany; Centre of Brain, Behaviour, and Metabolism (CBBM), University of Lübeck, Lübeck, Germany.
Thomas KarlasDivision of Gastroenterology, Medical Department II, University of Leipzig Medical Centre, Leipzig, Germany.
Arne DietrichDepartment of Visceral, Transplant, Thoracic and Vascular Surgery, University of Leipzig Medical Centre, Leipzig, Germany.
Martin GerickeLeipzig University, Institute of Anatomy, Leipzig, Germany.
Michael StumvollUniversity of Leipzig Medical Centre, Medical Department III-Endocrinology, Nephrology, Rheumatology, Leipzig, Germany; Helmholtz Institute for Metabolic Obesity and Vascular Research (HI-MAG), Helmholtz Zentrum München, University of Leipzig and University Hospital Leipzig, Leipzig, Germany.
Matthias BlüherUniversity of Leipzig Medical Centre, Medical Department III-Endocrinology, Nephrology, Rheumatology, Leipzig, Germany; Helmholtz Institute for Metabolic Obesity and Vascular Research (HI-MAG), Helmholtz Zentrum München, University of Leipzig and University Hospital Leipzig, Leipzig, Germany.
Martin von BergenDepartment of Molecular Systems Biology, Helmholtz-Centre for Environmental Research - UFZ, Leipzig, Germany; Institute of Biochemistry, Leipzig University, Leipzig, Germany; German Centre for Integrative Biodiversity Research (iDiv) Halle-Jena-Leipzig, Leipzig, Germany.
Kristin SchubertDepartment of Molecular Systems Biology, Helmholtz-Centre for Environmental Research - UFZ, Leipzig, Germany.
Peter KovacsUniversity of Leipzig Medical Centre, Medical Department III-Endocrinology, Nephrology, Rheumatology, Leipzig, Germany; Deutsches Zentrum für Diabetesforschung e.V., 85764, Neuherberg, Germany.
Rima M ChakarounUniversity of Leipzig Medical Centre, Medical Department III-Endocrinology, Nephrology, Rheumatology, Leipzig, Germany; Wallenberg Laboratory, Department of Molecular and Clinical Medicine and Sahlgrenska Centre for Cardiovascular and Metabolic Research, University of Gothenburg, Gothenburg, Sweden. Electronic address: rima.chakaroun@wlab.gu.se.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThis research investigates the determinants of circulating FGF21 levels in a cohort reflecting metabolic disease progression, examining the associations of circulating FGF21 with morphology and function of adipose tissue (AT), and with metabolic adjustments following metabolic surgery.

methodsWe measured serum FGF21 in 678 individuals cross-sectionally and in 189 undergoing metabolic surgery longitudinally. Relationships between FGF21 levels, AT histology, transcriptomes and proteomes, cardiometabolic risk factors, and post-surgery metabolic adjustments were assessed using univariate and multivariate analyses, causal mediation analysis, and network integration of AT transcriptomes and proteomes.

findingsFGF21 levels were linked to central adiposity, subclinical inflammation, insulin resistance, and cardiometabolic risk, and were driven by circulating leptin and liver enzymes. Higher FGF21 were linked with AT dysfunction reflected in fibro-inflammatory and lipid dysmetabolism pathways. Specifically, visceral AT inflammation was tied to both FGF21 elevation and liver dysfunction. Post-surgery, FGF21 peaked transitorily at three months. Mediation analysis highlighted an underlying increased AT catabolic state with elevated free fatty acids (FFA), contributing to higher liver stress and FGF21 levels (total effect of free fatty acids on FGF21 levels: 0.38, p < 0.01; proportion mediation via liver 32%, p < 0.01). In line with this, histological AT fibrosis linked with less pronounced FGF21 responses and reduced fat loss post-surgery (FFA and visceral AT fibrosis: rho = -0.31, p = 0.030; FFA and fat-mass loss: rho = 0.17, p = 0.020).

interpretationFGF21 reflects the liver's disproportionate metabolic stress response in both central adiposity and after metabolic surgery, with its dynamics reflecting an AT-liver crosstalk.

fundingThis work was supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) through CRC 1052, project number 209933838, CRC1382 and a Walther-Benjamin Fellowship and by a junior research grant by the Medical Faculty, University of Leipzig, and by the Federal Ministry of Education and Research (BMBF), Germany, FKZ: 01EO1501. Part of this work was supported by the European Union's Seventh Framework Program for research, technological development and demonstration under grant agreement HEALTH-F4-2012-305312 and by the CRC1382 and the Novo Nordisk Foundation and by the Deutsche Forschungsgemeinschaft (DFG, German Research foundation) project number 530364326.

Indexed as

Adipose TissueFibroblast Growth FactorsLiverObesityAdultBiomarkersCardiometabolic Risk FactorsCross-Sectional StudiesFemaleHumansMaleMiddle AgedBiomarkersFGF21 protein, humanfibroblast growth factor 21Fibroblast Growth FactorsAdipose tissueFGF21Insulin resistanceInter-organ crosstalkMetabolic diseaseMetabolic surgeryObesity

Identifiers

PMID39608059
PMCPMC11638646

What Socratic holds

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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 Socratic graph.