Evidence mapPaperPMID 40306359Full record

ArticleMolecular metabolism2025

14-3-3ζ allows for adipogenesis by modulating chromatin accessibility during the early stages of adipocyte differentiation.

Sabri A Rial, Zhipeng You, Alexis Vivoli, Fédéric Paré, Daphné Sean, Amal AlKhoury, Geneviève Lavoie, Mete Civelek, Aida Martinez-Sanchez, Philippe P Roux and 2 more

Abstract read
In one paragraph

Article in Molecular metabolism, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Article
  3. International journal of molecular sciences · 2025
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors.

Sabri A RialDepartment of Medicine, Université de Montréal, Montreal, QC, Canada; Cardiometabolic Axis, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC, Canada. Electronic address: ahmed.sabri.rial@umontreal.ca.
Zhipeng YouThe Neuro's Early Drug Discovery Unit (EDDU), McGill University, 3801 University Street, Montreal, QC, H3A 2B4, Canada.
Alexis VivoliDepartment of Medicine, Université de Montréal, Montreal, QC, Canada; Cardiometabolic Axis, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC, Canada.
Fédéric ParéCardiometabolic Axis, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC, Canada.
Daphné SeanDepartment of Medicine, Université de Montréal, Montreal, QC, Canada; Cardiometabolic Axis, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC, Canada.
Amal AlKhouryDepartment of Medicine, Université de Montréal, Montreal, QC, Canada; Cardiometabolic Axis, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC, Canada.
Geneviève LavoieInstitute for Research in Immunology and Cancer (IRIC), Université de Montréal, Montréal, QC, Canada; Department of Pathology and Cell Biology, Faculty of Medicine, Université de Montréal, Montréal, QC, Canada.
Mete CivelekDepartment of Biomedical Engineering, University of Virginia, Charlottesville, United States; Center for Public Health Genomics, University of Virginia, Charlottesville, VA, 22908, United States.
Aida Martinez-SanchezSection of Cell Biology and Functional Genomics, Department of Metabolism, Digestion and Reproduction, Imperial College London, Hammersmith Hospital, London, UK.
Philippe P RouxInstitute for Research in Immunology and Cancer (IRIC), Université de Montréal, Montréal, QC, Canada; Department of Pathology and Cell Biology, Faculty of Medicine, Université de Montréal, Montréal, QC, Canada.
Thomas M DurcanThe Neuro's Early Drug Discovery Unit (EDDU), McGill University, 3801 University Street, Montreal, QC, H3A 2B4, Canada.
Gareth E LimDepartment of Medicine, Université de Montréal, Montreal, QC, Canada; Cardiometabolic Axis, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC, Canada. Electronic address: gareth.lim@umontreal.ca.

Funding

NIDDK NIH HHS R01 DK118287
6 · The paper itself

Abstract

objectiveWe previously established the scaffold protein 14-3-3ζ as a critical regulator of adipogenesis and adiposity, but whether 14-3-3ζ exerted its regulatory functions in mature adipocytes or in adipose progenitor cells (APCs) remained unclear.

methodsTo decipher which cell type accounted for 14-3-3ζ-regulated adiposity, adipocyte- (Adipoq14-3-3ζKO) and APC-specific (Pdgfra14-3-3ζKO) 14-3-3ζ knockout mice were generated. To further understand how 14-3-3ζ regulates adipogenesis, Tandem Affinity Purification (TAP)-tagged 14-3-3ζ-expressing 3T3-L1 preadipocytes (TAP-3T3-L1) were generated with CRISPR-Cas9, and affinity proteomics was used to examine how the nuclear 14-3-3ζ interactome changes during the initial stages of adipogenesis. ATAC-seq was used to determine how 14-3-3ζ depletion modulates chromatin accessibility during differentiation.

resultsWe show a pivotal role for 14-3-3ζ in APC differentiation, whereby male and female Pdgfra14-3-3ζKO mice displayed impaired or potentiated weight gain, respectively, as well as fat mass. Proteomics revealed that regulators of chromatin remodeling, like DNA methyltransferase 1 (DNMT1) and histone deacetylase 1 (HDAC1), were significantly enriched in the nuclear 14-3-3ζ interactome and their activities were impacted upon 14-3-3ζ depletion. Enhancing DNMT activity with S-Adenosyl methionine rescued the differentiation of 14-3-3ζ-depleted 3T3-L1 cells. ATAC-seq revealed that 14-3-3ζ depletion impacted the accessibility of up to 1,244 chromatin regions corresponding in part to adipogenic genes, promoters, and enhancers during the initial stages of adipogenesis. Finally, 14-3-3ζ-regulated chromatin accessibility correlated with the expression of key adipogenic genes.

conclusionOur study establishes 14-3-3ζ as a crucial epigenetic regulator of adipogenesis and highlights the usefulness of deciphering the nuclear 14-3-3ζ interactome to identify novel pro-adipogenic factors and pathways.

Indexed as

14-3-3 ProteinsAdipocytesAdipogenesisChromatin3T3-L1 CellsAnimalsCell DifferentiationFemaleMaleMiceMice, Inbred C57BLMice, Knockout14-3-3 ProteinsChromatinYwhaz protein, mouse14-3-3ζAdipogenesisAdipogenic genesChromatin accessibilityEnergy homeostasisEpigenetic regulation

Identifiers

PMID40306359
PMCPMC12136713

What Socratic holds

Textmetadata
LicenceCC BY-NC
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.