Adipocyte fatty acid binding protein AFABP is a 15 kDa member of the intracellular fatty acid binding protein (FABP) family, which is known for the ability to bind fatty acids and related compounds (bile acids or retinoids) in an internal cavity. AFABP is expressed in a differentiation-dependent fashion in adipocytes and is a critical gene in the regulation of the biological function of these cells . In mice, targeted mutations in AFABP provide significant protection from hyperinsulinemia and insulin resistance in the context of both dietary and genetic obesity. Adipocytes obtained from AFABP-deficient mice also have reduced efficiency of lipolysis in vitro and in vivo, and these mice exhibited moderately improved systemic dyslipidemia. Recent studies also demonstrated AFABP expression in macrophages upon differentiation and activation. In these cells, AFABP modulates inflammatory responses and cholesterol ester accumulation, and total or macrophage-specific AFABP deficiency confers dramatic protection against atherosclerosis in the apoE-/- mice. These results indicate a central role for AFABP in the development of major components of the metabolic syndrome through its distinct actions in adipocytes and macrophages.