Obesity has reached pandemic proportions worldwide and continues to increase alarmingly, making it urgent to understand the molecular mechanisms that regulate energy metabolism, as well as novel signals secreted by adipose tissue under both physiological and pathological conditions. Recently, extracellular vesicles (EVs) have emerged as key mediators of tissue-to-tissue communication, transporting RNA, proteins and lipids that influence inflammation, metabolism and other cellular functions. This thesis investigates the role of EVs in obesity, focusing on how vesicles secreted by different tissues (adipocytes, hepatocytes, macrophages) contribute to metabolic alterations such as insulin resistance and inflammation. Through in vitro and in vivo experimental models, the composition and functional effects of EVs have been analysed using advanced isolation and proteomic analysis techniques. The results show that EVs from obese white adipocytes (obesesomes) and steatotic hepatocytes (steatosomes) exacerbate insulin resistance and promote inflammation. In contrast, EVs from activated brown adipocytes (heatosomes) promote thermogenesis and improve insulin sensitivity, suggesting their therapeutic potential in the treatment of obesity. In addition, specific proteins were identified in EVs that could serve as biomarkers for the diagnosis and monitoring of obesity and its comorbidities, such as hepatic steatosis, as well as therapeutic targets, especially those related to brown adipocyte thermogenesis. In conclusion, EVs play a crucial role in interorgan communication and modulation of obesity and its associated diseases. Current findings suggest their potential for personalised therapies and monitoring of treatment efficacy, although further research is needed to optimise their clinical application.
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