PuSH - Publikationsserver des Helmholtz Zentrums München

Frendo-Cumbo, S.* ; Zareifi, D.* ; Bigay, J.* ; Dias Araújo, A.R.* ; Lapp, A.* ; Hansen, M.* ; Reindl, T.P.* ; Engelmann, B.* ; Klingelhuber, F. ; Cordeddu, L.* ; Elmastas, M.* ; Jalkanen, J.* ; Renzi, G.* ; Buvry, O.* ; Debayle, D.* ; Allos, H.* ; López Yus, M.* ; Weinbrenner, S. ; Schormair, K.* ; Jamialahmadi, O.* ; Kerr, A.G.* ; Romeo, S.* ; Rolle-Kampczyk, U.* ; von Bergen, M.* ; Massier, L. ; Krahmer, N. ; Gautier, R.* ; Antonny, B.* ; Rydén, M.* ; Mejhert, N.*

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

Nat. Commun. 17:9458 (2026)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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.
Altmetric
Weitere Metriken?
[➜Einloggen]
Zusatzinfos bearbeiten [➜Einloggen]
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Zeitschrift Nature Communications
Quellenangaben Band: 17, Heft: 1, Seiten: , Artikelnummer: 9458 Supplement: ,
Verlag Springer
Verlagsort London
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes and Obesity (IDO)
Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG)
Förderungen Vetenskapsrådet (Swedish Research Council)