Adipose tissue ceramides: emerging lipid components of extracellular vesicles and their influence on metabolic dysregulation

Adipose tissue dysfunction is at the interphase between obesity and impaired metabolic health. Increased lipid spillover is a key mechanism by which adipose tissue dysfunction contributes to systemic metabolic dysregulation. This, in turn, leads to the accumulation of lipotoxic lipid species, such as ceramides, within metabolically active tissue not suited for lipid storage tissues thereby fueling insulin resistance. However, the buildup of ceramides also occurs in the adipose tissue of individuals with obesity where these sphingolipids may disrupt energy metabolism, insulin sensitivity and affect adipose tissue secretome, compromising systemic metabolic health. This review will provide an updated overview on the contribution of ceramides to adipose tissue dysfunction, with a particular focus on the onset of insulin resistance. Additionally, this manuscript will focus on the involvement of ceramides in modulating extracellular vesicle (EVs) secretion from the white adipose tissue and their role as bioactive components of EV lipidome able to discern individuals based on their metabolic status.