Proteomic Profiling of Plasma- and Gut-Derived Extracellular Vesicles in Obesity

Abstract

Obesity entails metabolic alterations across multiple organs, highlighting the role of inter-organ communication in its pathogenesis. Extracellular vesicles (EVs) are communication agents in physiological and pathological conditions, and although they have been associated with obesity comorbidities, their protein cargo in this context remains largely unknown. To decipher the messages encapsulated in EVs, we isolated plasma-derived EVs from a diet-induced obese murine model. Obese plasma EVs exhibited a decline in protein diversity while control EVs revealed significant enrichment in protein-folding functions, highlighting the importance of proper folding in maintaining metabolic homeostasis. Previously, we revealed that gut-derived EVs’ proteome holds particular significance in obesity. Here, we compared plasma and gut EVs and identified four proteins exclusively present in the control state of both EVs, revealing the potential for a non-invasive assessment of gut health by analyzing blood-derived EVs. Given the relevance of post-translational modifications (PTMs), we observed a shift in chromatin-related proteins from glycation to acetylation in obese gut EVs, suggesting a regulatory mechanism targeting DNA transcription during obesity. This study provides valuable insights into novel roles of EVs and protein PTMs in the intricate mechanisms underlying obesity, shedding light on potential biomarkers and pathways for future research.

A Pilot Study on the Proteomics Profile of Serum Exosome-Enriched Extracellular Vesicles from Normal versus Individuals with Obesity-Related Insulin Resistance

“…Another study has shown that transforming growth factor beta 1 (TGFBI) in circulating EVs may facilitate monitoring the T2D status in obese patients, and EV-mimecan (aka osteoglycin) may be useful to track visceral obesity [7]. Proteomics analysis of exosomes from mouse plasma has revealed an upregulation of two proteins (immunoglobulins) and downregulation of 10 proteins (14-3-3 protein isoforms, proteasome subunits, and others) in mice with diet-induced obesity [8]. Proteomics analysis has also been performed in adipocytes of human subjects which revealed that changes in proteins related to lipid metabolism and unfolded protein response discriminate insulinresistant and insulin-sensitive individuals with unequal adiposity [9].…”