Evidence map›Paper›PMID 41402426›Full record

ArticleScientific reports2025

Bioavailable human metabolites from TOTUM-448 (plant-based formulation) maintain liver cell functionality in a hyperlipidic context that drives MASLD onset.

Fabien Wauquier, Vivien Chavanelle, Annie Bouchard-Mercier, Line Boutin-Wittrant, Yolanda F Otero, Stéphanie Krisa, Josep Valls, Florian Le Joubioux, Bruno Pereira, Véronique Roux and 9 more

Abstract read
In one paragraph

Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. 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

19 authors.

Fabien WauquierFaculté de Médecine, Clinic'n'Cell SAS, 28 place Henri Dunant, Clermont-Ferrand, 63001, France.
Vivien ChavanelleValbiotis, 20 rue Henri et Gilberte Goudier, Riom, 63200, France.
Annie Bouchard-MercierValbiotis, 20 rue Henri et Gilberte Goudier, Riom, 63200, France.
Line Boutin-WittrantFaculté de Médecine, Clinic'n'Cell SAS, 28 place Henri Dunant, Clermont-Ferrand, 63001, France.
Yolanda F OteroValbiotis, 20 rue Henri et Gilberte Goudier, Riom, 63200, France.
Stéphanie KrisaUniversité de Bordeaux-INRAE-INP-ISVV, 210 Chem. de Leysotte, Villenave-d'Ornon, 33140, France.
Josep VallsMetaboHUB, Bordeaux Metabolome, 210 Chem. de Leysotte, Villenave-d'Ornon, 33140, France.
Florian Le JoubiouxValbiotis, Zone Industrielle des 4 Chevaliers, Bâtiment 12 F, Rue Paul Vatine, Perigny, 17180, France.
Bruno PereiraBiostat Unit, DRCI, CHU, Clermont-Ferrand, 63000, France.
Véronique RouxCIC INSERM 1405/Plateforme d'Investigation Clinique CHU Gabriel Montpied, Clermont-Ferrand, 63000, France.
Nicolas MacianCIC INSERM 1405/Plateforme d'Investigation Clinique CHU Gabriel Montpied, Clermont-Ferrand, 63000, France.
Gisèle PickeringCIC INSERM 1405/Plateforme d'Investigation Clinique CHU Gabriel Montpied, Clermont-Ferrand, 63000, France.
Véronique SaponeValbiotis, Zone Industrielle des 4 Chevaliers, Bâtiment 12 F, Rue Paul Vatine, Perigny, 17180, France.
Murielle CazaubielValbiotis, Zone Industrielle des 4 Chevaliers, Bâtiment 12 F, Rue Paul Vatine, Perigny, 17180, France.
Auriane BronDigestive Environment and Health, Université Clermont Auvergne, UMR 454 MEDIS UCA-INRAE, Microbiology, Clermont-Ferrand, France.
Sébastien PeltierValbiotis, Zone Industrielle des 4 Chevaliers, Bâtiment 12 F, Rue Paul Vatine, Perigny, 17180, France.
Stéphanie BlanquetDigestive Environment and Health, Université Clermont Auvergne, UMR 454 MEDIS UCA-INRAE, Microbiology, Clermont-Ferrand, France.
Pascal SirventValbiotis, 20 rue Henri et Gilberte Goudier, Riom, 63200, France.
Yohann WittrantFaculté de Médecine, Clinic'n'Cell SAS, 28 place Henri Dunant, Clermont-Ferrand, 63001, France. yohann.wittrant@inrae.fr.

Funding

Agence Nationale de la Recherche Labcom MIMETiv (ANR, ANR-22-LCV1-0003-01)Bordeaux Metabolome Facility and the MetaboHUB ANR11-INBS-0010Région Auvergne-Rhône-Alpes Pack Ambition Recherche 2021 MICROMETiv
6 · The paper itself

Abstract

Lipotoxic and inflammatory environment drives metabolic dysfunction-associated steatotic liver disease (MASLD) onset. As most conventional treatments present adverse side effects, alternative options such as preventive nutritional interventions have been developed, though further clinical validation is needed. In this study, we conducted an innovative ex vivo clinical investigation to examine how circulating metabolites generated after oral intake of TOTUM-448 (a plant-based, polyphenol-rich formulation) may influence hepatocyte function. UHPLC-MS/MS analysis confirmed and characterized the bioavailable polyphenol metabolites present in human serum. This metabolite-enriched serum was further used to treat HepG2 hepatocytes, with or without palmitate pretreatment (250 µM). The effects of TOTUM-448-derived metabolites on hepatocytes were evaluated by monitoring cell viability, lipid metabolism, inflammation, oxidative stress, and endoplasmic reticulum (ER) stress, all of which are central features of MASLD. Treated hepatocytes exhibited resistance to palmitate-induced lipotoxic stress, showing reduced intracellular lipid accumulation. TOTUM-448-derived metabolites also prevented the palmitate-induced upregulation of inflammatory gene expression. Additionally, while palmitate strongly upregulated CHOP and XBP1 mRNA expression as well as ATF6 and Caspase-3 activities, the presence of TOTUM-448-derived metabolites restored these ER stress markers to normal levels.

Indexed as

Fatty LiverHepatocytesLiverPlant ExtractsPolyphenolsCell SurvivalEndoplasmic Reticulum StressHep G2 CellsHumansLipid MetabolismMaleOxidative StressPalmitatesPalmitatesPlant ExtractsPolyphenolsClinical trialEx vivoHuman hepatocytesHuman metabolitesLipotoxic stressMASLDOxidative stressPlant extract

Identifiers

PMID41402426
PMCPMC12824265

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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.