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Key Words: FABP4 Ⅲ heart failure Ⅲ adipocytes Ⅲ metabolic syndrome O besity is a major risk factor in the development of the metabolic syndrome and cardiovascular diseases and seems to be directly related to heart failure independently of other risk factors. 1 Indeed, a direct relationship between elevated body mass index and increased risk for heart failure has been demonstrated, without evidence of a threshold. 2 Several potential mechanisms are under discussion to explain this correlation, including hemodynamic changes with cardiac overload and left ventricular remodeling and lipid accumulation into the myocardium, leading to lipoapoptosis in cardiomyocytes. 3 These mechanisms, however, do not fully explain the development of heart dysfunction in obese subjects.Adipocytes are known to produce and release a wide variety of bioactive molecules into the bloodstream. 4 Based on these data, we have recently investigated whether secretory products from human adipocytes affect cardiac contractile function in an in vitro system of isolated rat cardiomyocytes. We have demonstrated that mature human adipocytes release substances that strongly and acutely suppress the contraction of cardiomyocytes by attenuating intracellular Ca 2ϩ levels. 5 Our previous findings have revealed a hitherto unknown acute depressant effect of adipocyte-derived factors on cardiac contraction, suggesting a new direct role of adipose tissue in the pathogenesis of myocardium dysfunction.Based on this initial work, we have further characterized cardiodepressant activity by fractionating adipocyte secretory products according to molecular weight and proteomic analysis, identifying adipocyte fatty acid-binding protein (FABP4) as the active agent. Fatty acid-binding proteins (FABPs) are members of a highly conserved family of cytosolic proteins with a molecular mass of 14 to 15 kDa found in different cell types, showing a high affinity for long-chain fatty acids and other hydrophobic ligands. 6 FABP4 is predominantly expressed in adipose tissue, and accounts for Ϸ1% of total cytosolic protein in human adipose tissue. 7 Cytoplasmic FABP4 is involved in trafficking intra-

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