Publication Details |
| Category | Text Publication |
| Reference Category | Journals |
| DOI | 10.1038/s41467-026-77280-y |
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| Title (Primary) | Functional annotation of insulin-responsive genes in human adipocytes reveals PLCXD1 as a lipid storage regulator |
| Author | 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. |
| Source Titel | Nature Communications |
| Year | 2026 |
| Department | MOLTOX |
| Volume | 17 |
| Page From | art. 9458 |
| Language | englisch |
| Topic | T9 Healthy Planet |
| Data and Software links | https://doi.org/10.17632/3bs5f8mvbs.1 |
| Supplements | Supplement 1 Supplement 2 Supplement 3 Supplement 4 Supplement 5 Supplement 6 Supplement 7 Supplement 8 Supplement 9 |
| 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. |
| 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. (2026): Functional annotation of insulin-responsive genes in human adipocytes reveals PLCXD1 as a lipid storage regulator Nat. Commun. 17 , art. 9458 10.1038/s41467-026-77280-y |
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