{
  "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.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 30,
  "authors": [
    {
      "name": "Scott Frendo-Cumbo"
    },
    {
      "name": "Danae Zareifi"
    },
    {
      "name": "Joëlle Bigay"
    },
    {
      "name": "Ana Rita Dias Araújo"
    },
    {
      "name": "Alina Lapp"
    },
    {
      "name": "Mattias Hansen"
    },
    {
      "name": "Teresa P Reindl"
    },
    {
      "name": "Beatrice Engelmann"
    },
    {
      "name": "Felix Klingelhuber"
    },
    {
      "name": "Lina Cordeddu"
    },
    {
      "name": "Merve Elmastas"
    },
    {
      "name": "Jutta Jalkanen"
    },
    {
      "name": "Gianluca Renzi"
    },
    {
      "name": "Océane Buvry"
    },
    {
      "name": "Delphine Debayle"
    },
    {
      "name": "Hanin Allos"
    },
    {
      "name": "Marta López Yus"
    },
    {
      "name": "Sophie Weinbrenner"
    },
    {
      "name": "Katharina Schormair"
    },
    {
      "name": "Oveis Jamialahmadi"
    },
    {
      "name": "Alastair G Kerr"
    },
    {
      "name": "Stefano Romeo"
    },
    {
      "name": "Ulrike Rolle-Kampczyk"
    },
    {
      "name": "Martin von Bergen"
    },
    {
      "name": "Lucas Massier"
    },
    {
      "name": "Natalie Krahmer"
    },
    {
      "name": "Romain Gautier"
    },
    {
      "name": "Bruno Antonny"
    },
    {
      "name": "Mikael Rydén"
    },
    {
      "name": "Niklas Mejhert"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/82pwzx98ehj03.bib",
  "cited_by": 1,
  "doi": "10.1038/s41467-026-77280-y",
  "fulltext_url": null,
  "id": "82pwzx98ehj03",
  "issns": [
    "2041-1723",
    "2041-1723"
  ],
  "landing_url": "https://hal.science/hal-05762903v1",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "hal",
      "0.sdv"
    ],
    [
      "openalex",
      "1303|Lipid metabolism and biosynthesis"
    ]
  ],
  "openalex": "W7207582152",
  "pdf_url": "https://www.nature.com/articles/s41467-026-77280-y.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-03",
  "publisher": "Nature Publishing Group",
  "ris": "https://research.draconitic.com/paper/82pwzx98ehj03.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:40Z",
      "native_id": "hal-05762903",
      "source": "hal",
      "url": "https://hal.science/hal-05762903v1"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1303|Lipid metabolism and biosynthesis",
      "subfield": "enzymology-metabolism"
    }
  ],
  "title": "Functional annotation of insulin-responsive genes in human adipocytes reveals PLCXD1 as a lipid storage regulator",
  "title_text": "Functional annotation of insulin-responsive genes in human adipocytes reveals PLCXD1 as a lipid storage regulator",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:40Z",
  "url": "https://research.draconitic.com/paper/82pwzx98ehj03",
  "venue": "Nature Communications",
  "versions": []
}