Dataset Information

Seipin Governs Caveolin-1 Trafficking Through Modulating Sphingolipid-Glycerolipid Balance

ABSTRACT:

Dysregulation of Caveolin-1 (CAV1), a key component of caveolae, leads to pleiotropic disorders; yet, the mechanisms controlling its trafficking remain unclear. Here, we show that the lipid droplet (LD) biogenesis factor seipin controls CAV1 localization. Seipin deficiency in mice and HeLa cells resulted in the accumulation of saturated lipids and ceramides, disrupting the membrane order of the trans-Golgi network (TGN). This impaired CAV1 trafficking to the plasma membrane, reduced caveolae formation, and redirected CAV1 to LDs - an effect also observed in seipin-deficient patient fibroblasts. We reproduced this phenotype in wild-type cells by supplementing them with palmitate or ceramide, or by inhibiting stearoyl-CoA desaturase 1, which suggests that accumulating saturated lipids are the root cause. Inhibiting fatty acid synthase in seipin knockout cells rescued CAV1 localization. Our findings indicate that seipin modulates lipid partitioning between glycerolipids and sphingolipids, which is critical for maintaining TGN function in CAV1 sorting and trafficking.

INSTRUMENT(S): Liquid Chromatography MS -

PROVIDER: MTBLS12759 | MetaboLights | 2025-07-22

REPOSITORIES: MetaboLights

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	a_MTBLS12759_LC-MS___metabolite_profiling-1.txt	Txt
	a_MTBLS12759_LC-MS___metabolite_profiling-2.txt	Txt
	a_MTBLS12759_LC-MS___metabolite_profiling.txt	Txt
	i_Investigation.txt	Txt
	m_MTBLS12759_LC-MS___metabolite_profiling-1_v2_maf.tsv	Tabular

Items per page:

1 - 5 of 8

Similar Datasets

Project description:Background: Prolonged exposure to elevated free fatty acids induces β-cell failure (lipotoxicity) and contributes to the pathogenesis of type 2 diabetes. In vitro exposure of β-cells to the saturated free fatty acid palmitate is a valuable model of lipotoxicity, reproducing features of β-cell failure observed in type 2 diabetes. In order to map the β-cell response to lipotoxicity, we combined RNA-sequencing of palmitate-treated human islets with iTRAQ proteomics of insulin-secreting INS-1E cells following a time course exposure to palmitate. Results: Crossing transcriptome and proteome of palmitate-treated β-cells revealed 85 upregulated and 122 downregulated genes at both transcript and protein level. Pathway analysis identified lipid metabolism, oxidative stress, amino-acid metabolism and cell cycle pathways among the most enriched palmitate-modified pathways. Palmitate induced gene expression changes compatible with increased free fatty acid mitochondrial import and β-oxidation, decreased lipogenesis and modified cholesterol transport. Palmitate modified genes regulating endoplasmic reticulum (ER) function, ER-to-Golgi transport and ER stress pathways. Furthermore, palmitate modulated cAMP/protein kinase A (PKA) signaling, inhibiting expression of PKA anchoring proteins and downregulating the GLP-1 receptor. SLC7 family amino-acid transporters were upregulated in response to palmitate but this induction did not contribute to β-cell demise. To unravel critical mediators of lipotoxicity upstream of the palmitate-modified genes, we identified overrepresented transcription factor binding sites and performed network inference analysis. These identified LXR, PPARα, FOXO1 and BACH1 as key transcription factors orchestrating the metabolic and oxidative stress responses to palmitate. Conclusions: This is the first study to combine transcriptomic and sensitive time course proteomic profiling of palmitate-exposed β-cells. Our results provide comprehensive insight into gene and protein expression changes, corroborating and expanding beyond previous findings. The identification of critical drivers and pathways of the β-cell lipotoxic response points to novel therapeutic targets for type 2 diabetes.

Dataset Information

Seipin Governs Caveolin-1 Trafficking Through Modulating Sphingolipid-Glycerolipid Balance

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets