Gene expression in visceral adipocytes in metabolically healthy and unhealthy obesity: A cross-sectional analysis of associations with cardiometabolic components.

ObjectiveVisceral adipose tissue (VAT) produces several adipokines; however, VAT adipocytes' gene expression has not been related with cardio-metabolic components. The present study aimed to explore associations between gene expression in human primary VAT adipocytes' and cardio-metabolic components in subjects who live with Metabolically Unhealthy Obesity (MUO) compared with subjects who live with Metabolically Healthy Obesity (MHO).MethodsCross-sectional study of patients who live with obesity, who underwent bariatric/metabolic surgery.ResultsForty-five patients (18 MHO and 27 MUO) aged 44 years, main co-morbidities Diabetes and Hypertension, were analyzed. MUO showed younger age and higher cardio-metabolic risk, as well as larger adipocyte´s sizes. Primary cultured adipocytes were isolated from trans-surgical VAT sample, then cDNA was analyzed for the expression of 92 genes, further distributed as MUO vs. MHO and clustered according to their linkage with cardio-metabolic components. Higher expression of genes like EDN1, IL-6, ADIPOQ, GSTA2, TGFβ, WNT3A, KDR, MAPK3, vWF (p<0.04); as well as reduced NOS2, PDGFA, HAMP and RARRES2 (p<0.01) were observed across clusters of hyperglycemia, hypertension, dyslipidaemia, and central obesity, broadly implicating pathways related to inflammation, oxidative stress, endothelial dysfunction, insulin resistance, and vascular regulation.ConclusionFindings from the present exploratory analysis show that cardio-metabolic risk is associated to VAT adipocytes' gene expression; particularly those genes related to oxidative stress, insulin resistance, inflammation, endothelial dysfunction, athero-thrombosis, and lower vasodilation. Further longitudinal and mechanistic studies are required to clarify the directionality and clinical significance of these associations.