Small lipid-binding proteins in regulating endothelial and vascular functions: focusing on adipocyte fatty acid binding protein and lipocalin-2

Dysregulated production of adipokines from adipose tissue plays a critical role in the development of obesity-associated cardiovascular abnormalities. A group of adipokines, including adipocyte fatty acid binding protein (A-FABP) and lipocalin-2, possess specific lipid-binding activity and are up-regulated in obese human subjects and animal models. They act as lipid chaperones to promote lipotoxicity in endothelial cells and cause endothelial dysfunction under obese conditions. However, different small lipid-binding proteins modulate the development of vascular complications in distinctive manners, which are partly attributed to their specialized structural features and functionalities. By focusing on A-FABP and lipocalin-2, this review summarizes recent advances demonstrating the causative roles of these newly identified adipose tissue-derived lipid chaperones in obesity-related endothelial dysfunction and cardiovascular complications. The specific lipid-signalling mechanisms mediated by these two proteins are highlighted to support their specialized functions. In summary, A-FABP and lipocalin-2 represent potential therapeutic targets to design drugs for preventing vascular diseases associated with obesity.