Ultrastructural characterization of white adipocytes in a mouse model with enhanced sequestration of fatty acids in adipose tissue

Sequestration of free fatty acids (FFA) inside white adipose tissue (WAT) may reduce plasma FFA levels and prevent lipotoxicity in other organs. However, it is poorly understood how WAT responds to this metabolic stress. As albumin promotes FFA release from WAT, and thus albumin deficiency should promote FFA sequestration, we studied albumin knockout (Alb^-/-) mice and their wildtype (WT) littermates (eight-week-old males). Transmission electron microscopy and molecular analyses were used for characterization. There was no significant difference between genotypes for WAT mass, adipocyte size or triacylglycerol (TAG) content. No signs of cell death were observed in Alb^-/- adipocytes, suggesting a tolerance to the metabolic challenge. Alb^-/- adipocytes exhibited a lower density of caveolae with smaller invagination depths, indicating a potential adaptation to reduce FFA transport. A significantly higher abundance of micro-lipid droplets was observed in Alb^-/- mice, which may result from a rapid substrate cycle with high lipolysis and re-esterification. In support of the ultrastructural phenotype, lipidomic analysis also demonstrated a significant difference between Alb^-/- and WT for TAG composition. Our results showed that when no albumin is present to facilitate FFA mobilization, WAT can chronically adapt to protect the adipocytes in both morphological and molecular manners.