Effect of the hepatic extracellular vesicles in inflammation-associated insulin resistance in non-alcoholic fatty liver disease

Resumen del trabajo presentado al 3rd GLOBAL NASH Congress and Metaboloc syndrom, diabetes and NAFLD Symposium, celebrados del 10 al 11 de febrero de 2020 en Londres.
Cell-to-cell communication by extracellular vesicles (EVs) is an emerging issue in non-alcoholic fatty liver disease (NAFLD). In this study we found higher EVs secretion, particularly exosomes, in hepatocytes and plasma from obese mice with NAFLD compared with the controls from lean mice. Moreover, both the uptake of NAFLD-exosomes by macrophages in culture and intravenous injection of NAFLD-exosomes in mice triggered NFκB activation and a proinflammatory response. Insulin resistance was induced in hepatocytes incubated with the secretome of macrophages treated with NAFLD exosomes and in cultured hepatocytes isolated from mice injected with NAFLD exosomes. Our results identified a novel molecular mechanism in the interactome hepatocyte-macrophagehepatocyte where NAFLD exosomes (circulating or hepatocyte-derived) induced inflammation and insulin resistance through macrophages inflammatory responses.