Considering that PA and Fetuin-A stimulate TLR4-dependent IL-1β secretion in islet macrophages [24] and that Hep-sEVs are enriched in both PA [7] and Fetuin-A (this study) under MASLD conditions, our results suggest that sEVs may act as shuttles of SFA or/and Fetuin-A and induce TLR4-dependent IL-1β secretion from both liver and islet macrophages, thereby promoting beta cell dysfunction and type 2 diabetes development. Here, IL1B is linked to type 2 diabetes mellitus.