Evidence map›Paper›PMID 40652248›Full record

ArticleJournal of biomedical science2025

Obesity induces phenotypic switching of gastric smooth muscle cells through the activation of the PPARD/PDK4/ANGPTL4 pathway.

Sanaa Dekkar, Kamilia Mahloul, Amandine Falco, Karidia Konate, Romane Pisteur, Sarah Maurel, Laurent Maïmoun, Norbert Chauvet, Prisca Boisguérin, David Nocca and 7 more

Abstract read
In one paragraph

Article in Journal of biomedical science, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
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

17 authors.

Sanaa DekkarPHYMEDEXP, University of Montpellier, INSERM, CNRS, Montpellier, France.
Kamilia MahloulPHYMEDEXP, University of Montpellier, INSERM, CNRS, Montpellier, France.
Amandine FalcoPHYMEDEXP, University of Montpellier, INSERM, CNRS, Montpellier, France.
Karidia KonatePHYMEDEXP, University of Montpellier, INSERM, CNRS, Montpellier, France.
Romane PisteurPHYMEDEXP, University of Montpellier, INSERM, CNRS, Montpellier, France.
Sarah MaurelIRSD, INSERM, INRAe, ENVT, UPS, University of Toulouse, Toulouse, France.
Laurent MaïmounPHYMEDEXP, University of Montpellier, INSERM, CNRS, Montpellier, France.
Norbert ChauvetPHYMEDEXP, University of Montpellier, INSERM, CNRS, Montpellier, France.
Prisca BoisguérinPHYMEDEXP, University of Montpellier, INSERM, CNRS, Montpellier, France.
David NoccaDepartment of Digestive Surgery, University Hospital of Montpellier, Montpellier, France.
Ariane SultanPHYMEDEXP, University of Montpellier, INSERM, CNRS, Montpellier, France.
Florian PallotLAPEC, University of Avignon, Avignon, France.
Guillaume WaltherLAPEC, University of Avignon, Avignon, France.
Nicolas CenacIRSD, INSERM, INRAe, ENVT, UPS, University of Toulouse, Toulouse, France.
Cyril BreukerPHYMEDEXP, University of Montpellier, INSERM, CNRS, Montpellier, France.
Sandrine FaurePHYMEDEXP, University of Montpellier, INSERM, CNRS, Montpellier, France.
Pascal de Santa BarbaraPHYMEDEXP, University of Montpellier, INSERM, CNRS, Montpellier, France. pascal.de-santa-barbara@inserm.fr.ORCID http://orcid.org/0000-0001-9040-2481

Funding

Agence Nationale de la Recherche 11-INBS-010Agence Nationale de la Recherche ANR #19-CE21-0003-01FIMATHO 2021-2023
6 · The paper itself

Abstract

backgroundClinical research has identified stomach dysmotility as a common feature of obesity. However, the specific mechanisms driving gastric emptying dysfunction in patients with obesity remain largely unknown. In this study, we investigated potential mechanisms by focusing on the homeostasis of gastric smooth muscle.

methodsAn obese mouse model was established using a high-fat diet (HFD). Immunofluorescence analysis and Western blotting were employed to assess smooth muscle status using stage-specific markers. An in vitro culture model of differentiated human gastric smooth muscle cells (SMCs) was treated with lipids, siRNA-peptide-based nanoparticles and pharmaceutical compounds. Global lipidomic and RNA sequencing analyses were performed. The findings were evaluated in patients with obesity, using gastric samples from individuals who underwent sleeve gastrectomy, to evaluate their clinical relevance.

resultsThe smooth muscle layers in gastric tissue from both mice fed on a HFD as well as patients with obesity exhibited altered differentiation status. Treatment of differentiated human gastric SMCs with lipids phenocopies these alterations and is associated with increased expression of PDK4 and ANGPTL4. Inhibition of PDK4 or ANGPTL4 upregulation prevents these lipid-induced modifications. PPARD activation stimulates PDK4 and ANGPTL4 upregulation, leading to SMC dedifferentiation. Notably, PDK4 and ANGPTL4 levels correlate with immaturity and alteration of gastric smooth muscle in patients with obesity.

conclusionsObesity triggers a phenotypic change in gastric SMCs, driven by the activation of the PPARD/PDK4/ANGPTL4 pathway. These mechanistic insights offer potential biomarkers for diagnosing stomach dysmotility in patients with obesity.

Indexed as

Angiopoietin-Like Protein 4Myocytes, Smooth MuscleObesityPyruvate Dehydrogenase Acetyl-Transferring KinaseAnimalsDiet, High-FatFemaleHumansMaleMiceMice, Inbred C57BLPhenotypeSignal TransductionStomachAngiopoietin-Like Protein 4ANGPTL4 protein, humanPDK4 protein, humanPyruvate Dehydrogenase Acetyl-Transferring KinaseImmaturityObesityPDK4/ANGPTL4/PPARD pathwaySmooth muscleStomach

Identifiers

PMID40652248
PMCPMC12254972

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.