Adipocyte Fatty Acid–Binding Protein Suppresses Cardiomyocyte Contraction: A New Link Between Obesity and Heart Disease

• Published in: Circulation research Vol. 105; no. 4; pp. 326 - 334
• Main Authors: Lamounier-Zepter, Valéria, Look, Christiane, Alvarez, Julio, Christ, Torsten, Ravens, Ursula, Schunck, Wolf-Hagen, Ehrhart-Bornstein, Monika, Bornstein, Stefan R., Morano, Ingo
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD American Heart Association, Inc 14.08.2009; Lippincott Williams & Wilkins
• Subjects: Action Potentials - drug effects; Adipocytes - secretion; Adult; Aged; Animals; Atherosclerosis - metabolism; Biological and medical sciences; Calcium - metabolism; Calcium Signaling - drug effects; Cardiology. Vascular system; Cells, Cultured; Diabetes Mellitus, Type 2 - metabolism; Dose-Response Relationship, Drug; Fatty Acid-Binding Proteins - isolation & purification; Fatty Acid-Binding Proteins - pharmacology; Fatty Acid-Binding Proteins - secretion; Female; Fundamental and applied biological sciences. Psychology; Heart; Heart failure, cardiogenic pulmonary edema, cardiac enlargement; Humans; Male; Medical sciences; Metabolic diseases; Metabolic Syndrome - metabolism; Middle Aged; Myocardial Contraction - drug effects; Myocytes, Cardiac - metabolism; Obesity; Obesity - metabolism; Rats; Rats, Wistar; Vertebrates: cardiovascular system; Endocrinopathy; Heart failure; Adipocyte; Obesity; Nutrition disorder; Lipids; Metabolic diseases; Cardiovascular disease; Metabolic syndrome; Fatty acids; Contraction; Binding protein; Vertebrata; Mammalia; FABP4; Heart disease; Circulatory system; adipocytes; Nutritional status; Heart cell
• ISSN: 0009-7330; 1524-4571; 1524-4571
• DOI: 10.1161/CIRCRESAHA.109.200501

RATIONALE:Adipocyte fatty acid–binding protein (FABP4) is a member of the intracellular lipid-binding protein family and is predominantly expressed in adipose tissue. Emerging evidence suggests that FABP4 plays a role in some aspects of the metabolic syndrome including the development of type 2 diabetes and atherosclerosis. We have recently reported that secretory products from human adipocytes directly and acutely depressed cardiac contractile function. OBJECTIVE:The purpose of this study was to identify this adipocyte-derived cardiodepressant factor. METHODS AND RESULTS:Through mass spectrometry and immunoblotting, we have identified this cardiodepressant factor as FABP4. FABP4 represents 1.8% to 8.1% of total protein secreted by adipocytes in extracellular medium. FABP4 acutely depressed shortening amplitude as well as intracellular systolic peak Ca in a dose-dependent manner in isolated rat cardiomyocytes. Heart-specific FABP isoform (FABP3) revealed a similar cardiodepressant effect. The N-terminal amino acids 1 to 20 of FABP4 could be identified as the most effective cardiodepressive domain. We could exclude any effect of FABP4 on action potential duration and L-type Ca current, suggesting a reduced excitation-contraction gain caused by FABP4 as the main inhibitory mechanism. CONCLUSION:We conclude that the release of FABP4 from adipocytes may be involved in the development of cardiac contractile dysfunction of obese subjects.