Suppression of endothelial ceramide de novo biosynthesis by Nogo-B contributes to cardiometabolic diseases.

ABSTRACT: Accrual of ceramides, membrane and bioactive sphingolipids, has been implicated in endothelial dysfunction preceding cardiometabolic diseases. Yet, direct in vivo evidence, underlying mechanisms, and pathological implications are lacking. Here we show that suppression of ceramides and sphingosine-1-phosphate (S1P), a product of ceramide degradation, are causally linked to endothelial dysfunction and activation, contributing to vascular and metabolic disorders in high fat diet fed (HFD) male mice. Mechanistically, the upregulation of Nogo-B and ORMDL proteins suppress ceramide de novo biosynthesis in endothelial cells (EC) of HFD mice, resulting in vascular and metabolic dysfunctions. Systemic and endothelial specific deletion of Nogo-B restore sphingolipid signaling and functions, lowers h

SUBMITTER: Rubinelli L 

PROVIDER: S-EPMC11862206 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature