Details

Autor(en) / Beteiligte

• Rodríguez-Calvo, Ricardo
• Girona, Josefa
• Rodríguez, Marina
• Samino, Sara
• Barroso, Emma
• de Gonzalo-Calvo, David
• Guaita-Esteruelas, Sandra
• Heras, Mercedes
• van der Meer, Rutger W.
• Lamb, Hildo J.
• Yanes, Oscar
• Correig, Xavier
• Llorente-Cortés, Vicenta
• Vázquez-Carrera, Manuel
• Masana, Lluis

Titel

Fatty acid binding protein 4 (FABP4) as a potential biomarker reflecting myocardial lipid storage in type 2 diabetes

Ist Teil von

• Metabolism, clinical and experimental, 2019-07, Vol.96, p.12-21

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2019

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. 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. 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. 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. •Serum FABP4 is associated with myocardial neutral lipid content in type 2 diabetic patients.•FABP4 increases intracellular lipid content and insulin resistance in HL-1 cells.•FABP4 induces insulin resistance and impairs glucose uptake in HL-1 cardiac cells.•BMS309403 reduces FABP4-induced metabolic impairment in HL-1 cells.