Transcriptomic profiling reveals sex-specific molecular signatures of adipose endothelial cells under obesogenic conditions

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) fromthewhite adipose tissue ofmale 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.

Automated summary

Female mice exhibit greater adipose angiogenesis and healthier adipose tissue compared to males when fed a high-fat diet. Transcriptome analysis reveals that female adipose endothelial cells (EC) have upregulated genes related to proliferation, oxidative phosphorylation, and chromatin remodeling, while male EC genes are enriched for inflammation and senescence-associated secretory. These sex-biased phenotypes of adipose EC are also observed in aged EC. Our findings provide insights into the molecular mechanisms that differentiate male and female EC responses to pathophysiological conditions.