Ricardo Rodríguez-Calvo1, Josefa Girona2, Marina Rodríguez2, Sara Samino3, Emma Barroso4, David de Gonzalo-Calvo5, Sandra Guaita-Esteruelas2, Mercedes Heras2, Rutger W van der Meer6, Hildo J Lamb6, Oscar Yanes3, Xavier Correig3, Vicenta Llorente-Cortés7, Manuel Vázquez-Carrera4, Lluis Masana8. 1. Vascular Medicine and Metabolism Unit, Research Unit on Lipids and Atherosclerosis, "Sant Joan" University Hospital, Universitat Rovira i Virgili, Institut de Investigació Sanitaria Pere Virgili (IISPV), Reus, Spain; Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), Institute of Health Carlos III, Madrid, Spain. Electronic address: ricardo.rodriguez@ciberdem.org. 2. Vascular Medicine and Metabolism Unit, Research Unit on Lipids and Atherosclerosis, "Sant Joan" University Hospital, Universitat Rovira i Virgili, Institut de Investigació Sanitaria Pere Virgili (IISPV), Reus, Spain; Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), Institute of Health Carlos III, Madrid, Spain. 3. Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), Institute of Health Carlos III, Madrid, Spain; Metabolomics Platform, Department of Electronic Engineering (DEEEA), Universitat Rovira i Virgili, Tarragona, Spain. 4. Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), Institute of Health Carlos III, Madrid, Spain; Pharmacology Unit, Department of Pharmacology, Toxicology and Therapeutic Chemistry, Faculty of Pharmacy and Food Sciences, Institut de Biomedicina de la Universidad de Barcelona (IBUB), University of Barcelona, Barcelona, Spain; Institut de Recerca Sant Joan de Déu (IR-SJD), Barcelona, Spain. 5. Lipids and Cardiovascular Pathology Group, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain; Network Spanish Biomedical Research Centre for Biomedical Research in Cardiovascular Diseases (CIBERCV), Institute of Health Carlos III, Madrid, Spain. 6. Department of Radiology, Leiden University Medical Centre, Leiden, the Netherlands. 7. Lipids and Cardiovascular Pathology Group, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain; Network Spanish Biomedical Research Centre for Biomedical Research in Cardiovascular Diseases (CIBERCV), Institute of Health Carlos III, Madrid, Spain; Biomedical Research Institute of Barcelona, CSIC, Barcelona, Spain. 8. Vascular Medicine and Metabolism Unit, Research Unit on Lipids and Atherosclerosis, "Sant Joan" University Hospital, Universitat Rovira i Virgili, Institut de Investigació Sanitaria Pere Virgili (IISPV), Reus, Spain; Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), Institute of Health Carlos III, Madrid, Spain. Electronic address: luis.masana@urv.cat.
Abstract
OBJECTIVE: Fatty acid binding protein 4 (FABP4) is an intracellular lipid chaperone involved in the crosstalk between adipose and peripheral tissues, and it contributes to widespread insulin resistance in cells, including cardiac cells. However, the role of this adipokine in regulating cardiac metabolism and myocardial neutral lipid content in patients with type 2 diabetes has not been elucidated. METHODS: The impact of circulating FABP4 on the cardiac neutral lipid content was measured by proton magnetic resonance spectroscopy (1H-MRS) in patients with type 2 diabetes. Additionally, circulating FABP4 and the cardiac triglyceride content were analysed in high-fat diet (HFD)-fed mice, and the impact of the exogenous FABP4 was explored in HL-1 cardiac cells. RESULTS: Serum FABP4 levels were higher in type 2 diabetic patients compared to healthy individuals. Circulating FABP4 levels were associated with myocardial neutral lipid content in type 2 diabetic patients. In HFD-fed mice, both serum FABP4 and myocardial triglyceride content were increased. In FABP4-challenged HL-1 cells, extracellular FABP4 increased intracellular lipid accumulation, which led to impairment of the insulin-signalling pathway and reduced insulin-stimulated glucose uptake. However, these effects were partially reversed by FABP4 inhibition with BMS309403, which attenuated the intracellular lipid content and improved insulin signalling and insulin-stimulated glucose uptake. CONCLUSIONS: Taken together, our results identify FABP4 as a molecule involved in diabetic/lipid-induced cardiomyopathy and indicate that this molecule may be an emerging biomarker for diabetic cardiomyopathy-related disturbances, such as myocardial neutral lipid accumulation. Additionally, FABP4 inhibition may be a potential therapeutic target for metabolic-related cardiac dysfunctions.
OBJECTIVE:Fatty acid binding protein 4 (FABP4) is an intracellular lipid chaperone involved in the crosstalk between adipose and peripheral tissues, and it contributes to widespread insulin resistance in cells, including cardiac cells. However, the role of this adipokine in regulating cardiac metabolism and myocardial neutral lipid content in patients with type 2 diabetes has not been elucidated. METHODS: The impact of circulating FABP4 on the cardiac neutral lipid content was measured by proton magnetic resonance spectroscopy (1H-MRS) in patients with type 2 diabetes. Additionally, circulating FABP4 and the cardiac triglyceride content were analysed in high-fat diet (HFD)-fed mice, and the impact of the exogenous FABP4 was explored in HL-1 cardiac cells. RESULTS: Serum FABP4 levels were higher in type 2 diabeticpatients compared to healthy individuals. Circulating FABP4 levels were associated with myocardial neutral lipid content in type 2 diabeticpatients. In HFD-fed mice, both serum FABP4 and myocardial triglyceride content were increased. In FABP4-challenged HL-1 cells, extracellular FABP4 increased intracellular lipid accumulation, which led to impairment of the insulin-signalling pathway and reduced insulin-stimulated glucose uptake. However, these effects were partially reversed by FABP4 inhibition with BMS309403, which attenuated the intracellular lipid content and improved insulin signalling and insulin-stimulated glucose uptake. CONCLUSIONS: Taken together, our results identify FABP4 as a molecule involved in diabetic/lipid-induced cardiomyopathy and indicate that this molecule may be an emerging biomarker for diabetic cardiomyopathy-related disturbances, such as myocardial neutral lipid accumulation. Additionally, FABP4 inhibition may be a potential therapeutic target for metabolic-related cardiac dysfunctions.
Authors: Beatrice von Jeinsen; Lisa Ritzen; Julia Vietheer; Claudia Unbehaun; Maren Weferling; Christoph Liebetrau; Christian W Hamm; Andreas Rolf; Till Keller Journal: Cardiovasc Diabetol Date: 2020-07-29 Impact factor: 9.951
Authors: Ricardo Rodríguez-Calvo; Sara Samino; Josefa Girona; Neus Martínez-Micaelo; Pere Ràfols; María García-Altares; Sandra Guaita-Esteruelas; Alexandra Junza; Mercedes Heras; Oscar Yanes; Xavier Correig; Lluis Masana Journal: Biomolecules Date: 2020-09-03