In vitro model of palmitate-induced NASH, lipotoxic hepatocytes release extracellular vesicles (EV) containing ceramides mainly in an endoplasmic reticulum sensor-dependent manner to promote macrophage chemotaxis, and the use of IRE1 inhibitors or knockdown of its expression level reduces NASH inflammation as well as release of EVs. This evidence concerns the gene ERN1 and metabolic dysfunction-associated steatohepatitis.