Single-cell profiling of vascular endothelial cells reveals progressive organ-specific vulnerabilities during obesity.

ABSTRACT: Obesity promotes diverse pathologies, including atherosclerosis and dementia, which frequently involve vascular defects and endothelial cell (EC) dysfunction. Each organ has distinct EC subtypes, but whether ECs are differentially affected by obesity is unknown. Here we use single-cell RNA sequencing to analyze transcriptomes of ~375,000 ECs from seven organs in male mice at progressive stages of obesity to identify organ-specific vulnerabilities. We find that obesity deregulates gene expression networks, including lipid handling, metabolic pathways and AP1 transcription factor and inflammatory signaling, in an organ- and EC-subtype-specific manner. The transcriptomic aberrations worsen with sustained obesity and are only partially mitigated by dietary intervention and weight loss. For exa

SUBMITTER: Bondareva O 

PROVIDER: S-EPMC9684070 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature