Adipocyte-specific fatty acid–binding protein (AFABP), also designated aP2 and FABP4, belongs to the fatty acid-binding protein super family whose members have relative molecular masses of ～15, 000, and it is exclusively expressed in differentiated adipocytes (1, 2). FABP4 is a predominant cytosolic protein of mature adipocytes, accounting for ～6 % of total cellular proteins. This protein may be an important regulator of systemic insulin sensitivity and lipid and glucose metabolism (1). Mice deficient in aP2/FABP4 are protected from development of hyperinsulinemia, hyperglycemia, and insulin resistance in the context of both dietary and genetic obesity (3, 4). Adipocytes obtained from aP2/FABP4-null mice had markedly reduced efficiency of lipolysis in vivo and in vitro (5, 6) and exhibited a 2- to 3-fold decrease in fatty acid release, suggesting that FABP4 mediates efflux of fatty acids in normal physiology (7).
Although the physiological consequences of aP2/FABP4 deficiency have been predominantly linked to changes in adipocytes, it has reported that the presence of aP2/FABP4 in macrophages (2, 8) and have shown that aP2/FABP4 expression can be induced by peroxisome proliferatoractivated receptor gamma (PPAR gamma) agonists (8), by toll-like receptor agonists (9), oxidized LDL (10), and the differentiation of monocytes to macrophages and can be suppressed by treatment with a cholesterol-lowering statin (11). In these cells, aP2/FABP4 modulates inflammatory cytokine production and cholesterol ester accumulation (12).
In apolipoprotein E-deficient mice, ablation of the aP2/FABP4 gene conferred remarkable protection against atherosclerosis, which commonly occurs in this rat strain (13, 14). Taken together, these animal studies demonstrate that aP2/FABP4, by integrating metabolic and inflammatory pathways, provides a key link between various components of metabolic syndrome. Moreover, Masato Furuhashi, M. et al. (2007) reported that an orally active small-molecule inhibitor of aP2/FABP4 is an effective therapeutic agent against severe atherosclerosis and type 2 diabetes in mouse models.