Extracellular Vesicles and Their Correlation with Inflammatory Factors in an Experimental Model of Steatotic Liver Disease Associated with Metabolic Dysfunction

• DOI: 10.1089/met.2023.0284
• Publication Date: 2024-03-18T19:57:32Z
• Authors: Melina Belén Kein...; Larisse Longo; Vitória Brum da S...; Fabrício Figueiró; Danieli Rosane Da...; Adriana Raffin Po...; Thalia Michele Vi...; Patrícia Luciana ...; Mário Reis Álvare...; Carolina Uribe-Cruz
• Keywords: Male; Inflammation; Diet, High-Fat; Rats; Choline Deficiency; Rats, Sprague-Dawley; Fatty Liver; Extracellular Vesicles; Disease Models, Animal; Liver; Non-alcoholic Fatty Liver Disease; Animals; Inflammation Mediators; Biomarkers

Background/Aims: Extracellular vesicles (EVs) are promising as a biomarker of metabolic dysfunction associated steatotic liver disease (MASLD). The objective is to study EVs and their involvement in MASLD concerning the disease's pathogenesis and progression characteristics. Methods: Male adult Sprague Dawley rats were randomly assigned into two experimental models of MASLD: MASLD-16 and MASLD-28, animals received a choline-deficient high-fat diet (CHFD) and Control-16 and Control-28, animals received a standard diet (SD) for 16 and 28 weeks, respectively. Biological samples from these animal models were used, as well as previously registered variables. EVs from hepatic tissue were characterized using confocal microscopy. EVs were isolated through differential ultracentrifugation from serum and characterized using NanoSight. The data from the EVs were correlated with biochemical, molecular, and histopathological parameters. Results: Liver EVs were identified through the flotillin-1 protein. EVs were isolated from the serum of all groups. There was a decrease of EVs concentration in MASLD-28 in comparison with Control-28 (P < 0.001) and a significant increase in EVs concentration in Control-28 compared with Control-16 (P < 0.001). There was a strong correlation between serum EVs concentration with hepatic gene expression of interleukin (Il)6 (r2 = 0.685, P < 0.05), Il1b (r2 = 0.697, P < 0.05) and tumor necrosis factor-alpha (Tnfa; r2 = 0.636, P < 0.05) in MASLD-16. Moreover, there was a strong correlation between serum EVs size and Il10 in MASLD-28 (r2 = 0.762, P < 0.05). Conclusion: The concentration and size of EVs correlated with inflammatory markers, suggesting their involvement in the systemic circulation, cellular communication, and development and progression of MASLD, demonstrating that EVs have the potential to serve as noninvasive biomarkers for MASLD diagnosis and prognosis.