Transcriptomic profiling reveals sex-specific molecular signatures of adipose endothelial cells under obesogenic conditions
Martina Rudnicki,
Alexandra Pislaru,
Omid Rezvan,
Eric Rullman,
Aly Fawzy,
Emmanuel Nwadozi,
Emilie Roudier,
Thomas Gustafsson,
Tara L. Haas
Affiliations
Martina Rudnicki
School of Kinesiology and Health Science & Muscle Health Research Centre, York University, Toronto, Canada; Corresponding author
Alexandra Pislaru
Department of Biology, York University, Toronto, Canada
Omid Rezvan
School of Kinesiology and Health Science & Muscle Health Research Centre, York University, Toronto, Canada
Eric Rullman
Department Laboratory Medicine, Clinical Physiology, Karolinska Institutet and Department Clinical Physiology, Karolinska University Hospital, Stockholm, Sweden
Aly Fawzy
School of Kinesiology and Health Science & Muscle Health Research Centre, York University, Toronto, Canada
Emmanuel Nwadozi
School of Kinesiology and Health Science & Muscle Health Research Centre, York University, Toronto, Canada
Emilie Roudier
School of Kinesiology and Health Science & Muscle Health Research Centre, York University, Toronto, Canada
Thomas Gustafsson
Department Laboratory Medicine, Clinical Physiology, Karolinska Institutet and Department Clinical Physiology, Karolinska University Hospital, Stockholm, Sweden
Tara L. Haas
School of Kinesiology and Health Science & Muscle Health Research Centre, York University, Toronto, Canada; Department of Biology, York University, Toronto, Canada; Corresponding author
Summary: Female mice display greater adipose angiogenesis and maintain healthier adipose tissue than do males upon high-fat diet feeding. Through transcriptome analysis of endothelial cells (EC) from the white adipose tissue of male and female mice high-fat-fed for 7 weeks, we found that adipose EC exhibited pronouncedly sex-distinct transcriptomes. Genes upregulated in female adipose EC were associated with proliferation, oxidative phosphorylation, and chromatin remodeling contrasting the dominant enrichment for genes related to inflammation and a senescence-associated secretory of male EC. Similar sex-biased phenotypes of adipose EC were detectable in a dataset of aged EC. The highly proliferative phenotype of female EC was observed also in culture conditions. In turn, male EC displayed greater inflammatory potential than female EC in culture, based on basal and tumor necrosis factor alpha-stimulated patterns of gene expression. Our study provides insights into molecular programs that distinguish male and female EC responses to pathophysiological conditions.
