Combined transcriptomics and metabolomics analyses of adipose tissue in obese subjects reveal pathways associated with insulin resistance

diabetes is a heterogeneous disease and various genetic and environmental components play a role in etiology of the disease. Understanding the metabolic profiles of tissues involved in etiology of the disease may provide us with insight into signatures associated with its function. Here we aim to identify metabolic signatures associated with insulin resistance (IR) in human adipose tissue using combined analyses of gene expression, metabolomics and human Genome scale metabolic networks (e.g., HMR). Our analyses for the genes associated with HOMA-IR found 62 genes to be significantly dysregulated (Padj < 0.05) in obese participants (N = 56). From the metabolic network based pathway analyses 27 metabolic pathways (Padj <0.05) were found to be dysregulated where 69 metabolites (Padj <0.05) were found to be up-regulated in association with IR. In addition we found a considerable overlap between the lipids represented on HMR and detected on our global Lipidomics UHPLC-QTOF platform. The reporter metabolites and pathways found in our represent putative markers for variation in insulin resistance among obese patients for further validation in metabolomics/Lipidomics studies.