Abstract
Obesity is associated with numerous deadly co-morbidities including cardiac failure, atherosclerosis, stroke, neurodegeneration, pulmonary arterial hypertension, thrombosis and diabetes. One common feature of these disorders is the presence of vascular defects. In this study, we analyzed how obesity impacts vascular endothelial cells throughout the body.
We undertook scRNA-seq analysis of ~350,000 endothelial cells (ECs) from the brain, lungs, heart, kidneys, liver, visceral adipose tissue and subcutaneous adipose tissue in mice at progressive stages of obesity and uncovered organ-specific vulnerabilities. Obesity deregulated gene networks including lipid handling, metabolic pathways, AP1 transcription factor and inflammatory signaling in an organ- and EC-subtype-specific manner. The transcriptomic aberrations worsened with sustained obesity, and were only partially mitigated by dietary intervention and weight loss. As such, dietary intervention substantially attenuated the dysregulation of liver, but not kidney, EC transcriptomes. Through integration of human GWAS, we identified a subset of vascular disease risk genes that are induced by obesity.
Our work catalogues the impact of obesity on the endothelium and reveals novel candidate targets for therapy.
The data are accessible in an interactive format below. For each dataset, the following 8 treatment groups and time points are available:
- Chow 3 months
- Western diet 3 months
- Chow 4 months
- Western diet 4 months
- Reversion: Western diet 3 months + chow diet 1 month
- Chow 6 months
- Western diet 6 months
- Reversion: Western diet 3 months + chow diet 3 months
