Integrative analysis of sex differences in adipose tissue gene expression

Sex differences in adipose tissue distribution and function are associated with cardiometabolic disease risk. While extensive research efforts have revealed sex differences in cell signaling and physiology, there is a relative dearth of information regarding the contribution of transcriptional regulation to sex differences in adipose function. We investigated sex‐dependent features of transcriptional regulation in subcutaneous adipose tissues using multiple publicly available omic‐scale gene expression data sets from geographically and ethnically diverse healthy human populations (N = 111–404 samples). Gene set enrichment analyses revealed that fatty acid metabolism, glycolysis, oxidative phosphorylation, and reactive oxygen species production pathways were enriched for differentially expressed genes (FDR < 0.1). We further identified a core set of 79 genes that were consistently differentially expressed in subcutaneous adipose tissue, but not other metabolic tissues (e.g., ELOVL3, FADS1, RORB, FDR < 0.05). A preponderance of these sex‐dependent genes exhibited expression correlations with metabolic traits that were measured in parallel with genes expression (e.g., LDL cholesterol, blood pressure, and body mass index). The genes that were positively correlated with deleterious metabolic traits were enriched for upregulation in males. Many of these results from humans were replicated in adipose tissue transcriptomic data from a population of 97 genetically diverse mouse strains. To further interrogate the molecular causes and consequences of sex‐dependent gene expression differences, we employed bioinformatic and network inference analyses. We identified putative upstream regulators of gene expression sex differences including PPARG and CEBPB. We identified subtle differences in gene expression coordination based on network analysis. A related but distinct aspect of sex differences in adipose function is that there are sex differences in the associations between genetic variants and body fat distribution‐related traits. Current efforts are underway to determine whether these sex‐dependent influences of genetics on adipose distribution could be mediated by influences on gene expression in adipose tissue, as suggested in the literature but not previously demonstrated. Our findings and related investigations have the potential to impact precision medicine approaches that account for the influences of sex on the development and perpetuation of cardiometabolic diseases. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .