Obesogenic diet disrupts tissue-specific mitochondrial gene signatures in the artery and capillary endothelium

Author:

Dunaway Luke S.1,Luse Melissa A.12,Nyshadham Shruthi1,Bulut Gamze1,Alencar Gabriel F.3,Chavkin Nicholas W.14ORCID,Cortese-Krott Miriam5ORCID,Hirschi Karen K.14,Isakson Brant E.12ORCID

Affiliation:

1. Robert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, Virginia, United States

2. Department of Molecular Physiology and Biological Physics, University of Virginia School of Medicine, Charlottesville, Virginia, United States

3. Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, Virginia, United States

4. Department of Cell Biology, University of Virginia School of Medicine, Charlottesville, Virginia, United States

5. Department of Cardiology, Pneumology and Angiology, Heinrich Heine University of Düsseldorf, Düsseldorf, Germany

Abstract

Using bulk and single-cell RNA sequencing on endothelial cells from adipose and mesentery, we found that an obesogenic diet induces a reduction in adipose endothelial oxidative phosphorylation gene expression, resulting in a phenotypic convergence of mesenteric and adipose endothelial cells. Furthermore, we found evidence that PPAR-γ drives this phenotypic shift. Mining of human data sets segregated based on body mass index supported these findings. These data point to novel mechanisms by which obesity induces endothelial dysfunction.

Funder

Lipedema Foundation

University of Virginia

HHS | NIH | National Heart, Lung, and Blood Institute

American Heart Association

Publisher

American Physiological Society

Subject

Genetics,Physiology

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