Abstracts and Commentaries: A new link between obesity and heart disease

s and Commentaries: A new link between obesity and heart disease Danielle Feuvray University of Paris-Sud 11 and CNRS UMR 8162, Marie Lannelongue Hospital, Le Plessis Robinson, France Correspondence: Danielle Feuvray, University of Paris-Sud 11 and CNRS UMR 8162, Marie Lannelongue Hospital, 92350 Le Plessis Robinson, France. e-mail: [email protected] Conflicts of interest: None. Adipocyte Fatty Acid-Binding Protein Suppresses Cardiomyocyte Contraction. A New Link Between Obesity and Heart Disease Lamounier-Zepter V, Look C, Alvarez J, et al. Circ. Res. 2009;105:326-334. Obesity 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. Indeed, a direct relationship between increased body mass index and increased risk for heart failure has been demonstrated. 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. These mechanisms, however, do not fully explain the development of heart dysfunction in obese individuals. Adipocytes are known to produce and release a wide variety of bioactive molecules into the bloodstream. On the basis of these data, the authors have recently demonstrated that mature human adipocytes release substances that strongly and acutely suppress the contraction of cardiomyocytes by attenuating intracellular Ca2þ concentrations. Their 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. The authors further characterized cardiodepressant activity by fractionating adipocyte secretory products according to molecular weight and proteomic analysis, identifying adipocyte fatty acid-binding protein 4 (FABP4) as the active agent. FABPs are members of a highly conserved family of cytosolic Heart Metab. 2010; 48:35–38 proteins showing a high affinity for long-chain fatty acids and other hydrophobic ligands. FABP4 is predominantly expressed in adipose tissue, and accounts for approximately 1% of total cytosolic protein in human adipose tissue. Cytoplasmic FABP4 is involved in trafficking intracellular fatty acids and other lipid signals by interaction with functional targets. In experimental animal models, FABP4 deficiency protects against the development of diabetes and atherosclerotic cardiovascular disease in both genetic and dietary forms of obesity. Humans with a functional genetic variant of the FABP4 gene, resulting in reduced adipose tissue expression of FABP4, have lower serum concentrations of triglycerides, and are at significantly reduced risk for type 2 diabetes and coronary artery disease. In a recent cross-sectional study, a correlation was observed between circulating concentrations of FABP4 and metabolic syndrome. Together, these clinical and experimental data support a key role for FABP4 in the development of metabolic and cardiovascular complications in obesity.