Changes of myocardial lipidomics profiling in a rat model of diabetic cardiomyopathy using UPLC/Q-TOF/MS analysis

Abstract

BackgroundDiabetic cardiomyopathy (DCM) is a serious cardiac dysfunction induced by changes in the structure and contractility of the myocardium that are initiated in part by alterations in energy substrates. The underlying mechanisms of DCM are still under controversial. The observation of lipids, especially lipidomics profiling, can provide an insight into the know the biomarkers of DCM. The aim of our research was to detect changes of myocardial lipidomics profiling in a rat model of diabetic cardiomyopathy.MethodsDiabetic cardiomyopathy was induced by feeding a high-sucrose/fat diet (HSFD) for 28 weeks and streptozotocin (30 mg/kg, intraperitoneally). The ultra-high-performance liquid chromatography (UPLC) coupled to quadruple time-of flight (QTOF) mass spectrometer was used to acquire and analyze the lipidomics profiling of myocardial tissue. Meanwhile, parameters of cardiac function were collected using cardiac catheterization, and the cardiac index was calculated, and fasting blood glucose and lipid levels were measured by an ultraviolet spectrophotometric method.ResultsWe detected 3023 positive ion peaks and 300 negative ion peaks. Levels of phosphatidylcholine (PC) (22:6/18:2), PC (22:6/18:1), PC (20:4/16:1), PC (16:1/18:3), phosphatidylethanolamine (PE) (20:4/18:2), and PE (20:4/16:0) were down-regulated, and PC (20:2/18:2), PC (18:0/16:0), and PC (20:4/18:0) were up-regulated in DCM model rats, when compared with control rats. Cardiac functions signed as values of left ventricular systolic pressure, maximal uprising velocity of left ventricular pressure and maximal decreasing velocity of left ventricular pressure were injured by 21–44%, and the cardiac index was increased by 25%, and fasting blood glucose and lipids were increased by 34–368%. Meanwhile, the cardiac lipid-related biomarkers have significant correlation with changes of cardiac function and cardiac index.ConclusionsUPLC/Q-TOF/MS analysis data suggested changes of some potential lipid biomarkers in the development of cardiac dysfunction and hypertrophy of diabetic cardiomyopathy, which may serve as potential important targets for clinical diagnosis and therapeutic intervention of DCM in the future.

Berberine Could Ameliorate Cardiac Dysfunction via Interfering Myocardial Lipidomic Profiles in the Rat Model of Diabetic Cardiomyopathy

“…Then, we used UPLC/Q-TOF/MS analyzed approach to explore the changes of myocardial lipidomic profiles in diabetic rats. And the results manifested that the cardiac lipid metabolites have remarkable correlation with changes of cardiac function and heart mass ratio (Dong et al, 2017 ).…”

“…The recent studies in DCM animal models suggested the important role of phospholipids (e.g., phosphatidylcholine and phosphatidylethanolamine) in the development of cardiac dysfunction and remodeling of DCM (Dong et al, 2017 ). We also found that berberine could protect against cardiac dysfunction induced by high caloric diet via promoting glucose transport and inhibiting cardiac lipid accumulation (Dong et al, 2011 ).…”

Lipidomic profiling of amniotic fluid and its application in fetal lung maturity prediction

“…The targeted lipid library applied in the metabolomic study was based on our existing lipid library which contains 151 lipids with known structures, including 88 PCs, 27 PEs, 23 SMs, and 13 Cers. There had been examples employing the targeted lipidomic approach in studies of other diseases such as schizophrenia, diabetic cardiomyopathy, and clear cell renal cell carcinoma . The raw data from LC‐HRMS were imported to the Skyline software (Windsor, UK) for the relative quantification of the lipid species based on the retention time and the accurate mass in the constructed polar lipids database (in‐house database).…”

Metabolic Profiling of the Diabetic Heart: Toward a Richer Picture

“…The development and progression of DbCM is associated with altered levels of specific lipid species in the myocardium, which has led to the suggestion that lipids might act as plasma-borne biomarkers for the condition. Shotgun lipidomic studies have often been used for this purpose (Han et al, 2005, 2007; Dong et al, 2017, 2018). PC, PE, and SM species are among the lipid classes identified as potential biomarkers for DbCM (Dong et al, 2017, 2018), with a number of species correlating with changes in cardiac function (Dong et al, 2017).…”

“…Shotgun lipidomic studies have often been used for this purpose (Han et al, 2005, 2007; Dong et al, 2017, 2018). PC, PE, and SM species are among the lipid classes identified as potential biomarkers for DbCM (Dong et al, 2017, 2018), with a number of species correlating with changes in cardiac function (Dong et al, 2017). Specifically, the species PC[22:6/18:2], PC[22:/18:1], PC[20:4/16:1], PE[20:4/18:2], and PE[20:4/16:0] were all found to be downregulated, and PC[20:2/18:2], PC[18:0/16:0], and PC[20:4/18:0] upregulated in the myocardium of a high-sucrose/fat diet +STZ rat model (Dong et al, 2017), with some perturbations in lipid profiles (e.g., PC[20:4/18:0]) being partially reversible upon treatment with the phytochemical berberine, the active ingredient of a traditional Chinese medicine used in the treatment of diabetes (Dong et al, 2018).…”