Untargeted and Targeted Proteomic Analysis of the Impact of Diabetes Mellitus on Two Adipose Tissue Depots and Blood of Obese Patients

Abstract

Background: Obesity has increased over the last years and it is one of the most common cardiovascular risk factors. In addition obesity is associated with the development of other metabolic disorders such as insulin resistance and type-2 diabetes mellitus (T2DM). Here, we have investigated two adipose tissue depots (AT) proteome and secreted serum proteins in obese patients to understand fat tissue characteristics in metabolic syndrome and T2DM.Methods: We used an untargeted proteomic approach to compare white AT of subcutaneous (SAT) and visceral (VAT) depots in type 3 obese patients. In silico analysis and bioinformatics were applied to proteomic data to gain systems biology information. By bead-based targeted multiplex assay system, we simultaneously detected and quantified multiple targets in qualified complex samples and analyzed the changes produced in the adipokine serum composition due to obesity and T2DM.Results: Protein composition in SAT and VAT showed significant differences. There was upregulation of proteins related with the endocrine regulation system in SAT, whereas proteins upregulated in VAT were related to metabolic disorders. VAT protein composition was more sensitive to the presence of diabetes than SAT. A pro-inflammatory state, caused by the secretion of cytokines and related adypokines, was observed in the serum protein composition of both obese and diabetic patients.Conclusions: Our results show a synergic alteration in the metabolic and inflammatory state in both VAT and serum due to the presence of diabetes, whereas changes in SAT were related with endocrine regulation.