内科学
内分泌学
糖尿病性心肌病
2型糖尿病
脂滴
胰岛素
胰岛素抵抗
脂质代谢
脂肪酸
甘油三酯
脂肪酸结合蛋白
医学
糖尿病
脂肪组织
心肌病
化学
生物化学
胆固醇
心力衰竭
基因
作者
Ricardo Rodríguez‐Calvo,Josefa Girona,M. Mar Rodríguez,Sara Samino,Emma Barroso,David de Gonzalo‐Calvo,Sandra Guaita‐Esteruelas,Mercedes Heras,R.W. van der Meer,Hildo J. Lamb,Óscar Yanes,X. Correig,Vicenta Llorente‐Cortés,Manuel Vázquez‐Carrera,L. Masana
标识
DOI:10.1016/j.metabol.2019.04.007
摘要
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.
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