Topinformationen

Vortrag von Dr. Niklas Mejhert

Vortragstitel: "Multiparametric screening reveals PLCXD1 as a regulator of insulin-stimulated lipid metabolism in human adipocytes"
Anlass: SFB Seminar
Beginn: 08.05.2025 - 16:15 Uhr
Ort: CellNanOs, 38/201

Über den Vortragenden: Dr. Niklas Mejhert forscht im Department of Medicine, Huddinge Karolinska Institutet Stockholm.

Insulin regulates adipocyte biology primarily through signaling pathways that control gene expression, yet many insulin-responsive targets remain poorly characterized. Here, we integrated three transcriptomic datasets to define a core set of insulin-regulated genes and assessed their functions in human adipocytes using a multiparametric lipid turnover screen. This revealed four gene clusters involved in biosynthesis, protein processing, glucose utilization, and lipid metabolism. Among lipid-related hits, phospholipase C X domain-containing protein-1 (PLCXD1) emerged as a regulator of insulin-stimulated lipogenesis, without affecting lipolysis or adipogenesis. PLCXD1 is transcriptionally induced by insulin via sterol regulatory element-binding proteins, and its induction was blunted in insulin resistance. Imaging and biochemical analyses showed that this atypical phospholipase localized to early endosomes and catalyzed phosphatidylinositol conversion into diacylglycerol. Site-directed mutagenesis identified residues required for enzymatic function but not endosomal localization. Our findings establish PLCXD1 as an insulin-responsive effector of lipid metabolism, with implications for adipocyte dysfunction in insulin resistance