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Bondareva, O. ; Rodriguez Aguilera, J.R. ; dos santos Oliveira, F. ; Liao, L. ; Rose, A. ; Gupta, A.* ; Singh, K.* ; Geier, F. ; Schuster, J. ; Boeckel, J.N.* ; Buescher, J.M.* ; Kohli, S.* ; Klöting, N. ; Isermann, B.* ; Blüher, M. ; Sheikh, B.

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

Nat. Metab. 4, 1591-1610 (2022)
Publ. Version/Full Text Research data DOI
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
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 example, dietary intervention substantially attenuates dysregulation of liver, but not kidney, EC transcriptomes. Through integration with human genome-wide association study data, we further identify a subset of vascular disease risk genes that are induced by obesity. Our work catalogs the impact of obesity on the endothelium, constitutes a useful resource and reveals leads for investigation as potential therapeutic targets.
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Publication type Article: Journal article
Document type Scientific Article
ISSN (print) / ISBN 2522-5812
e-ISSN 2522-5812
Quellenangaben Volume: 4, Issue: 11, Pages: 1591-1610 Article Number: , Supplement: ,
Publisher Springer
Publishing Place London
Reviewing status Peer reviewed
Institute(s) Helmholtz Institute for Metabolism, Obesity and Vascular Research (HI-MAG)
Grants Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH).