Whole‐Genome Transcriptomics of PBMC to Identify Biomarkers of Early Metabolic Risk in Apparently Healthy People with Overweight‐Obesity and in Normal‐Weight Subjects

Scope Peripheral blood mononuclear cells (PBMC) provide a useful and minimally invasive source of biomarkers. Here to identify PBMC transcriptomic biomarkers predictive of metabolic impairment related to increased adiposity is aimed. Methods and results The study analyzed the global PBMC transcriptome in metabolically healthy (normoglycemic) volunteers with overweight‐obesity (OW‐OB, n = 12), and in subjects with metabolically obese normal‐weight (MONW, n = 5) phenotype, in comparison to normal‐weight (NW, n = 12) controls. The study identifies 1072 differentially expressed genes (DEGs) in OW‐OB versus NW and 992 in MONW versus NW. Hierarchical clustering of the top 100 DEGs clearly distinguishes OW‐OB and MONW from NW. Remarkably, the OW‐OB and MONW phenotypes share 257 DEGs regulated in the same direction. The top up‐regulated gene CXCL8 , coding for interleukin 8, with a role in obesity‐related pathologies, is of special interest as a potential marker for predicting increased metabolic risk. CXCL8 expression is increased mainly in the MONW group and correlated directly with C‐reactive protein levels. Conclusions PBMC gene expression analysis of CXCL8 or a pool of DEGs may be used to identify early metabolic risk in an apparently healthy population regardless of their BMI, i.e., subjects with OW‐OB or MONW phenotype and to apply adequate and personalized nutritional preventive strategies.