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

ABSTRACT: Insulin regulates adipocyte biology partly by modulating gene expression, still many insulin-responsive targets remain uncharacterized. Here, we integrate three transcriptomic datasets to define insulin-regulated genes and assess 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 transcriptionally induced by insulin via sterol regulatory element-binding proteins, an induction impaired in insulin resistance. This atypical phospholipase is genetically linked to increased fat mass, localizes to early endosomes and catalyzes phosphatidylinositol conversion into diacylglycerol, which appears necessary for lipid storage. Furthermore, we identify residues required for enzymatic activity without affecting localization. Proteomic assessment was performed in PLCXD1 depleted adipocytes to gain insight into PLCXD1 function and assess compensatory protein changes. Altogether, our results uncover PLCXD1 as an insulin-regulated enzyme coupling intracellular membrane signaling to lipid metabolism across physiological and pathological states.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Fat Cell

SUBMITTER: Natalie Krahmer

LAB HEAD: Natalie Krahmer

PROVIDER: PXD072248 | Pride | 2026-06-02

REPOSITORIES: pride

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			Action	DRS
	20230903_FK_Scott_KOs_10.raw	Raw
	20230903_FK_Scott_KOs_11.raw	Raw
	20230903_FK_Scott_KOs_12.raw	Raw
	20230903_FK_Scott_KOs_13.raw	Raw
	20230903_FK_Scott_KOs_14.raw	Raw

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