Role of Extracellular Vesicles in Metabolic Regulation and Obesity-Related Diseases

Extracellular vesicles (EVs) exhibit a mechanism of intercellular communication that play a role in both health and disease. However, their specific functions in regulating metabolism and their connections to metabolic disorders like obesity are still not well understood.

In this study, the researchers isolated EVs through a series of ultracentrifugation steps from mouse adipocytes treated with palmitate or oleic acid, as well as from visceral and subcutaneous adipose tissue of obese bariatric surgery donors (referred to as obesesomes), and from steatotic human hepatocytes (termed steatosomes). They conducted functional experiments to assess the impact of these EVs on inflammation and metabolic processes in target cells, including human and mouse macrophages and hepatocytes, utilizing techniques such as ELISA, RT-PCR, and immunodetection. The isolated EVs were characterized for their quantity, size, and tetraspanin profile using NTA and SP-IRIS, and their protein contents were analyzed through both qualitative (DDA) and quantitative (DIA-SWATH) proteomics with LC-MS/MS. Proteins identified were further verified by acquiring EVs on specially designed chips using SP-IRIS.

The study findings revealed that EVs play a significant role in the communication between obese adipocytes and immune cells in adipose tissue, as well as between steatotic and healthy hepatocytes in relation to the progression of fatty liver disease. The experts also highlighted the interactions between EVs from obese adipose tissue and the liver, which contribute to metabolic dysregulation associated with obesity.

Specifically, obesesomes were shown to enhance inflammation and the release of pro-inflammatory cytokines when interacting with macrophages, significantly affecting insulin resistance and altering lipid and glucose metabolism in hepatocytes. The most deleterious effects were observed with EVs from palmitate-treated adipocytes and those from human visceral fat. Furthermore, steatosomes secreted by fatty liver hepatocytes caused insulin resistance and disrupted metabolic processes in healthy hepatocytes, indicating their role in the development of Metabolic Associated Steatotic Liver Disease (MASLD). Proteomic analysis of steatosomes identified proteins linked to liver disease, suggesting that these EVs serve as valuable markers for the early detection and progression of MASLD.

Source: Lago-Baameiro N, Camino T, Vazquez-Durán A, Sueiro A, Couto I, Santos F, Baltar J, Falcón-Pérez JM, Pardo M. Intra and inter-organ communication through extracellular vesicles in obesity: functional role of obesesomes and steatosomes. J Transl Med. 2025 Feb 20;23(1):207. doi: 10.1186/s12967-024-06024-7. PMID: 39979938; PMCID: PMC11844161.

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