Circulating Micro-RNAs and isomiRs are putative biomarkers for an obesity phenotype with high visceral adipose tissue inflammation
2Software and Information Systems Engineering, Ben Gurion University, Israel
Background: Individuals with obesity differ in the degree of increased cardiometabolic health risk imposed by obesity, which is known to associate with the extent of visceral adipose tissue (VAT) inflammation. Thus, assessing VAT inflammation may assist in patients’ risk stratification/classification, but VAT is not accessible for direct sampling in the non-surgical patient. We hypothesized that circulating miRNAs and specific isomiRs could serve as clinically-accessible biomarkers of obesity phenotype with high VAT-inflammation.
Methods: In patients (n=35) with obesity undergoing elective abdominal surgery, VAT inflammation was assessed by the mRNA expression of TNF-alpha, IL-6 and CCL2. Circulating and VAT small-RNAs were analyzed by Next Generation Sequencing providing resolution of specific miRNA variants (isomiRs). Patients were stratified according to low/high VAT inflammation.
Results: Individual clinical parameters of the patients didn’t significantly differ between the groups, but those with high VAT-inflammation trended to have lower HDL, insulin resistance, and lower adiponectin/leptin ratio. 54 circulating miRNAs associated with high VAT inflammation. Among them, hsa-miRNA-106b-3p and hsa-miRNA-181b-5p, known to be related with CV risk and inflammation, were differentially up-regulated in high-VAT-inflammation. A subset of VAT-inflammation -associated circulating miRNAs also correlated with their abundance in VAT, suggesting that VAT could constitute a major source for their abundance in the circulation. Analysis of circulating isomiRs suggested that stronger correlations with VAT inflammation can be obtained when considering the full repertoire of circulating miRNAs/isomiRs.
Conclusions: Circulating-miRNAs including hsa-miR-106b-3p and hsa-miR-181b-5p and isomiRs reflective of VAT-inflammation are potential biomarker tools for better personalizing care of patients with obesity.