Comparison of Plasma Exosome Proteomes Between Obese and Non-Obese Patients with Type 2 Diabetes Mellitus.

Purpose: Obesity is considered a promoter of type 2 diabetes mellitus (T2DM). However, the underlying mechanism remains unclear. This study aimed to identify plasma exosome differentially expressed proteins (DEPs) that are potentially involved in the development of obesity-related T2DM. Methods: Exosomes were isolated from the plasma of obese and non-obese T2DM patients (n = 10 for each group). A label-free quantitative mass spectrometry analysis was applied to identify plasma exosome DEPs in obese patients compared with non-obese patients, followed by bioinformatics analysis including GO annotation, KEGG analysis, subcellular localization prediction, transcription factor analysis, and protein-protein interaction (PPI) prediction. Results: We identified 2 significantly upregulated proteins (C9 and PON1) and 5 significantly downregulated proteins (HPX, A1BG, CFHR1, ANG, and CALM) in obese patients compared with those in non-obese patients. KEGG analysis demonstrated that the insulin signaling pathway was one of the pathways that significantly correlated with the DEPs. The DEPs were primarily localized in the extracellular space (5 out of 7). HMG-box and NF-Y beta might regulate the transcription of the DEPs. C9, PON1, HPX, and CFHR1 were present in the PPI network. Conclusion: The plasma exosome DEPs are potentially responsible for the development of obesity-related T2DM possibly through the insulin signaling pathway and the interaction with other proteins. Our study may guide future research direction toward the pathogenesis of obesity-related T2DM.