Evidence map›Paper›PMID 42693141›Full record

ArticleNature communications2026

Functional annotation of insulin-responsive genes in human adipocytes reveals PLCXD1 as a lipid storage regulator.

Scott Frendo-Cumbo, Danae Zareifi, Joëlle Bigay, Ana Rita Dias Araújo, Alina Lapp, Mattias Hansen, Teresa P Reindl, Beatrice Engelmann, Felix Klingelhuber, Lina Cordeddu and 20 more

Abstract read
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

30 authors.

Scott Frendo-CumboDepartment of Medicine (Huddinge), Karolinska Institutet, Stockholm, Sweden.ORCID http://orcid.org/0000-0002-9047-4650
Danae ZareifiDepartment of Medicine (Huddinge), Karolinska Institutet, Stockholm, Sweden.ORCID http://orcid.org/0000-0003-2108-4955
Joëlle BigayUMR 7275, Institut de Pharmacologie Moléculaire et Cellulaire, Université Côte d'Azur, CNRS and Inserm, Sophia Antipolis, Valbonne, France.ORCID http://orcid.org/0000-0002-7487-3416
Ana Rita Dias AraújoUMR 7275, Institut de Pharmacologie Moléculaire et Cellulaire, Université Côte d'Azur, CNRS and Inserm, Sophia Antipolis, Valbonne, France.ORCID http://orcid.org/0000-0003-3729-747X
Alina LappDepartment of Medicine (Huddinge), Karolinska Institutet, Stockholm, Sweden.ORCID http://orcid.org/0009-0004-8240-2333
Mattias HansenDepartment of Medicine (Huddinge), Karolinska Institutet, Stockholm, Sweden.
Teresa P ReindlDepartment of Medicine (Huddinge), Karolinska Institutet, Stockholm, Sweden.
Beatrice EngelmannDepartment of Molecular Toxicology, Helmholtz-Centre for Environmental Research - UFZ, Leipzig, Germany.ORCID http://orcid.org/0000-0002-8807-9651
Felix KlingelhuberInstitute for Diabetes and Obesity, Helmholtz Zentrum München, Neuherberg, Germany.
Lina CordedduDepartment of Medicine (Huddinge), Karolinska Institutet, Stockholm, Sweden.
Merve ElmastasDepartment of Medicine (Huddinge), Karolinska Institutet, Stockholm, Sweden.ORCID http://orcid.org/0000-0002-1346-5080
Jutta JalkanenDepartment of Medicine (Huddinge), Karolinska Institutet, Stockholm, Sweden.ORCID http://orcid.org/0000-0002-0219-1096
Gianluca RenziDepartment of Medicine (Huddinge), Karolinska Institutet, Stockholm, Sweden.
Océane BuvryUMR 7275, Institut de Pharmacologie Moléculaire et Cellulaire, Université Côte d'Azur, CNRS and Inserm, Sophia Antipolis, Valbonne, France.
Delphine DebayleUMR 7275, Institut de Pharmacologie Moléculaire et Cellulaire, Université Côte d'Azur, CNRS and Inserm, Sophia Antipolis, Valbonne, France.
Hanin AllosDepartment of Medicine (Huddinge), Karolinska Institutet, Stockholm, Sweden.
Marta López YusAdipocyte and Fat Biology Laboratory (AdipoFat), Translational Research Unit, University Hospital Miguel Servet, Zaragoza, Spain.ORCID http://orcid.org/0000-0002-5822-9823
Sophie WeinbrennerHelmholtz Institute for Metabolic, Obesity, and Vascular Research (HI-MAG) of the Helmholtz Zentrum München at the University of Leipzig and University Hospital Leipzig, Leipzig, Germany.ORCID http://orcid.org/0009-0002-4719-9953
Katharina SchormairDepartment of Medicine (Huddinge), Karolinska Institutet, Stockholm, Sweden.
Oveis JamialahmadiDepartment of Medicine (Huddinge), Karolinska Institutet, Stockholm, Sweden.
Alastair G KerrDepartment of Medicine (Huddinge), Karolinska Institutet, Stockholm, Sweden.ORCID http://orcid.org/0000-0003-2085-1542
Stefano RomeoDepartment of Medicine (Huddinge), Karolinska Institutet, Stockholm, Sweden.ORCID http://orcid.org/0000-0001-9168-4898
Ulrike Rolle-KampczykDepartment of Molecular Toxicology, Helmholtz-Centre for Environmental Research - UFZ, Leipzig, Germany.ORCID http://orcid.org/0000-0002-7728-6284
Martin von BergenDepartment of Molecular Toxicology, Helmholtz-Centre for Environmental Research - UFZ, Leipzig, Germany.ORCID http://orcid.org/0000-0003-2732-2977
Lucas MassierDepartment of Medicine (Huddinge), Karolinska Institutet, Stockholm, Sweden.ORCID http://orcid.org/0000-0002-6199-2643
Natalie KrahmerInstitute for Diabetes and Obesity, Helmholtz Zentrum München, Neuherberg, Germany.ORCID http://orcid.org/0000-0003-4063-7367
Romain GautierUMR 7275, Institut de Pharmacologie Moléculaire et Cellulaire, Université Côte d'Azur, CNRS and Inserm, Sophia Antipolis, Valbonne, France.ORCID http://orcid.org/0000-0001-6678-132X
Bruno AntonnyUMR 7275, Institut de Pharmacologie Moléculaire et Cellulaire, Université Côte d'Azur, CNRS and Inserm, Sophia Antipolis, Valbonne, France.ORCID http://orcid.org/0000-0002-9166-8668
Mikael Rydén *Department of Medicine (Huddinge), Karolinska Institutet, Stockholm, Sweden. mikael.ryden@ki.se.ORCID http://orcid.org/0000-0003-4785-1876
Niklas Mejhert *Department of Medicine (Huddinge), Karolinska Institutet, Stockholm, Sweden. niklas.mejhert@ki.se.ORCID http://orcid.org/0000-0003-1785-833X

Funding

Vetenskapsrådet (Swedish Research Council) 00
6 · The paper itself

Abstract

Insulin-driven gene regulation is central to adipocyte function, but the roles of many of these genes in lipid metabolism remain unclear. Here, we integrate three transcriptomic datasets to identify insulin-responsive genes and define their functions in human adipocytes using a multiparametric lipid turnover screen. Our results reveal four major clusters involved in metabolic regulation, transcription, stress responses, and lipid metabolism. Among lipid-related hits, phospholipase C X domain-containing protein-1 (PLCXD1) emerges as a regulator of insulin-stimulated lipogenesis, without affecting lipolysis or adipogenesis. PLCXD1 is induced by insulin via sterol regulatory element-binding proteins, a response attenuated in insulin-resistant states. This atypical phospholipase is genetically associated with fat mass-related traits, localizes to early endosomes and catalyzes phosphatidylinositol conversion into diacylglycerol. Through structure-function analyses, we show that PLCXD1 catalytic activity is required for insulin-stimulated lipogenesis. Altogether, our results uncover PLCXD1 as an insulin-regulated enzyme linking endosomal phosphoinositide metabolism to lipid storage in adipocytes.

Indexed as

AdipocytesInsulinLipid MetabolismAdipogenesisEndosomesGene Expression RegulationHumansLipogenesisLipolysisPhosphatidylinositolsInsulinPhosphatidylinositols

Identifiers

PMID42693141
PMCPMC13542105

What Socratic holds

Textmetadata
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.