Skip to main content
Top
Published in: Diabetology & Metabolic Syndrome 1/2017

Open Access 01-12-2017 | Research

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

Authors: Shifen Dong, Rong Zhang, Yaoyue Liang, Jiachen Shi, Jiajia Li, Fei Shang, Xuezhou Mao, Jianning Sun

Published in: Diabetology & Metabolic Syndrome | Issue 1/2017

Login to get access

Abstract

Background

Diabetic 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.

Methods

Diabetic 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.

Results

We 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.

Conclusions

UPLC/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.
Literature
1.
go back to reference Overgaard AJ, Weir JM, De Souza DP, Tull D, Haase C, Meikle PJ, et al. Lipidomic and metabolomic characterization of a genetically modified mouse model of the early stages of human type 1 diabetes pathogenesis. Metabolomics. 2016;12:13.CrossRefPubMed Overgaard AJ, Weir JM, De Souza DP, Tull D, Haase C, Meikle PJ, et al. Lipidomic and metabolomic characterization of a genetically modified mouse model of the early stages of human type 1 diabetes pathogenesis. Metabolomics. 2016;12:13.CrossRefPubMed
2.
go back to reference Yach D, Stuckler D, Brownell KD. Epidemiologic and economic consequences of the global epidemics of obesity and diabetes. Nat Med. 2006;12:62–6.CrossRefPubMed Yach D, Stuckler D, Brownell KD. Epidemiologic and economic consequences of the global epidemics of obesity and diabetes. Nat Med. 2006;12:62–6.CrossRefPubMed
4.
go back to reference Anand SS, Yusuf S. Stemming the global tsunami of cardiovascular disease. Lancet. 2011;377:529–32.CrossRefPubMed Anand SS, Yusuf S. Stemming the global tsunami of cardiovascular disease. Lancet. 2011;377:529–32.CrossRefPubMed
5.
go back to reference Rahman S, Rahman T, Ismail AA, Rashid AR. Diabetes-associated macrovasculopathy: pathophysiology and pathogenesis. Diabetes Obes Metab. 2007;9:767–80.CrossRefPubMed Rahman S, Rahman T, Ismail AA, Rashid AR. Diabetes-associated macrovasculopathy: pathophysiology and pathogenesis. Diabetes Obes Metab. 2007;9:767–80.CrossRefPubMed
7.
go back to reference Loffroy R, Bernard S, Serusclat A, Boussel L, Bonnefoy E, D’Athis P, et al. Noninvasive assessment of the prevalence and characteristics of coronary atherosclerotic plaques by multidetector computed tomography in asymptomatic type 2 diabetic patients at high risk of significant coronary artery disease: a preliminary study. Arch Cardiovasc Dis. 2009;102:607–15.CrossRefPubMed Loffroy R, Bernard S, Serusclat A, Boussel L, Bonnefoy E, D’Athis P, et al. Noninvasive assessment of the prevalence and characteristics of coronary atherosclerotic plaques by multidetector computed tomography in asymptomatic type 2 diabetic patients at high risk of significant coronary artery disease: a preliminary study. Arch Cardiovasc Dis. 2009;102:607–15.CrossRefPubMed
8.
go back to reference Trachanas K, Sideris S, Aggeli C, Poulidakis E, Gatzoulis K, Tousoulis D, et al. Diabetic cardiomyopathy: from pathophysiology to treatment. Hellenic J Cardiol. 2014;55:411–21.PubMed Trachanas K, Sideris S, Aggeli C, Poulidakis E, Gatzoulis K, Tousoulis D, et al. Diabetic cardiomyopathy: from pathophysiology to treatment. Hellenic J Cardiol. 2014;55:411–21.PubMed
9.
go back to reference Bertoni AG, Hundley WG, Massing MW, Bonds DE, Burke GL, Goff DC Jr. Heart failure prevalence, incidence, and mortality in the elderly with diabetes. Diabetes Care. 2004;27:699–703.CrossRefPubMed Bertoni AG, Hundley WG, Massing MW, Bonds DE, Burke GL, Goff DC Jr. Heart failure prevalence, incidence, and mortality in the elderly with diabetes. Diabetes Care. 2004;27:699–703.CrossRefPubMed
10.
go back to reference Aneja A, Tang WH, Bansilal S, Garcia MJ, Farkouh ME. Diabetic cardiomyopathy: insights into pathogenesis, diagnostic challenges, and therapeutic options. Am J Med. 2008;121:748–57.CrossRefPubMed Aneja A, Tang WH, Bansilal S, Garcia MJ, Farkouh ME. Diabetic cardiomyopathy: insights into pathogenesis, diagnostic challenges, and therapeutic options. Am J Med. 2008;121:748–57.CrossRefPubMed
11.
go back to reference Tarquini R, Lazzeri C, Pala L, Rotella CM, Gensini GF. The diabetic cardiomyopathy. Acta Diabetol. 2011;48:173–81.CrossRefPubMed Tarquini R, Lazzeri C, Pala L, Rotella CM, Gensini GF. The diabetic cardiomyopathy. Acta Diabetol. 2011;48:173–81.CrossRefPubMed
12.
go back to reference Miki T, Yuda S, Kouzu H, Miura T. Diabetic cardiomyopathy: pathophysiology and clinical features. Heart Fail Rev. 2013;18:149–66.CrossRefPubMed Miki T, Yuda S, Kouzu H, Miura T. Diabetic cardiomyopathy: pathophysiology and clinical features. Heart Fail Rev. 2013;18:149–66.CrossRefPubMed
13.
go back to reference Poornima IG, Parikh P, Shannon RP. Diabetic cardiomyopathy: the search for a unifying hypothesis. Circ Res. 2006;98:596–605.CrossRefPubMed Poornima IG, Parikh P, Shannon RP. Diabetic cardiomyopathy: the search for a unifying hypothesis. Circ Res. 2006;98:596–605.CrossRefPubMed
14.
go back to reference Chavali V, Tyagi SC, Mishra PK. Predictors and prevention of diabetic cardiomyopathy. Diabetes Metab Syndr Obes. 2013;6:151–60.PubMedPubMedCentral Chavali V, Tyagi SC, Mishra PK. Predictors and prevention of diabetic cardiomyopathy. Diabetes Metab Syndr Obes. 2013;6:151–60.PubMedPubMedCentral
15.
go back to reference D’Souza K, Nzirorera C, Kienesberger PC. Lipid metabolism and signaling in cardiac lipotoxicity. Biochim Biophys Acta. 2016;1860:1513–24.CrossRef D’Souza K, Nzirorera C, Kienesberger PC. Lipid metabolism and signaling in cardiac lipotoxicity. Biochim Biophys Acta. 2016;1860:1513–24.CrossRef
16.
go back to reference Kralik PM, Ye G, Metreveli NS, Shem X, Epstein PN. Cardiomyocyte dysfunction in models of type 1 and type 2 diabetes. Cardiovasc Toxicol. 2005;5:285–92.CrossRefPubMed Kralik PM, Ye G, Metreveli NS, Shem X, Epstein PN. Cardiomyocyte dysfunction in models of type 1 and type 2 diabetes. Cardiovasc Toxicol. 2005;5:285–92.CrossRefPubMed
17.
go back to reference Dong SF, Hong Y, Liu M, Hao YZ, Yu HS, Liu Y, et al. Berberine attenuates cardiac dysfunction in hyperglycemic and hypercholesterolemic rats. Eur J Pharmacol. 2011;660:368–74.CrossRefPubMed Dong SF, Hong Y, Liu M, Hao YZ, Yu HS, Liu Y, et al. Berberine attenuates cardiac dysfunction in hyperglycemic and hypercholesterolemic rats. Eur J Pharmacol. 2011;660:368–74.CrossRefPubMed
18.
go back to reference Luo M, Guan X, Luczak ED, Lang D, Kutschke W, Gao Z, et al. Diabetes increases mortality after myocardial infarction by oxidizing CaMKII. J Clin Invest. 2013;123:1262–74.CrossRefPubMedPubMedCentral Luo M, Guan X, Luczak ED, Lang D, Kutschke W, Gao Z, et al. Diabetes increases mortality after myocardial infarction by oxidizing CaMKII. J Clin Invest. 2013;123:1262–74.CrossRefPubMedPubMedCentral
19.
go back to reference Brugger B. Lipidomics: analysis of the lipid composition of cells and subcellular organelles by electrospray ionization mass spectrometry. Annu Rev Biochem. 2014;83:79–98.CrossRefPubMed Brugger B. Lipidomics: analysis of the lipid composition of cells and subcellular organelles by electrospray ionization mass spectrometry. Annu Rev Biochem. 2014;83:79–98.CrossRefPubMed
20.
go back to reference Rolim AE, Henrique-Araujo R, Ferraz EG, de Araujo Alves Dultra FK, Fernandez LG. Lipidomics in the study of lipid metabolism: current perspectives in the omic sciences. Gene. 2015;554:131–9.CrossRefPubMed Rolim AE, Henrique-Araujo R, Ferraz EG, de Araujo Alves Dultra FK, Fernandez LG. Lipidomics in the study of lipid metabolism: current perspectives in the omic sciences. Gene. 2015;554:131–9.CrossRefPubMed
21.
go back to reference Gudbjarnason S. Dynamics of n-3 and n-6 fatty acids in phospholipids of heart muscle. J Intern Med Suppl. 1989;731:117–28.CrossRefPubMed Gudbjarnason S. Dynamics of n-3 and n-6 fatty acids in phospholipids of heart muscle. J Intern Med Suppl. 1989;731:117–28.CrossRefPubMed
22.
go back to reference Benediktsdottir VE, Curvers J, Gudbjarnason S. Time course of alterations in phospholipid fatty acids and number of beta-adrenoceptors in the rat heart during adrenergic stimulation in vivo. J Mol Cell Cardiol. 1999;31:1105–15.CrossRefPubMed Benediktsdottir VE, Curvers J, Gudbjarnason S. Time course of alterations in phospholipid fatty acids and number of beta-adrenoceptors in the rat heart during adrenergic stimulation in vivo. J Mol Cell Cardiol. 1999;31:1105–15.CrossRefPubMed
23.
go back to reference Skuladottir GV, Schioth HB, Gudbjarnason S. Polyunsaturated fatty acids in heart muscle and alpha 1-adrenoceptor binding properties. Biochim Biophys Acta. 1993;1178:49–54.CrossRefPubMed Skuladottir GV, Schioth HB, Gudbjarnason S. Polyunsaturated fatty acids in heart muscle and alpha 1-adrenoceptor binding properties. Biochim Biophys Acta. 1993;1178:49–54.CrossRefPubMed
25.
go back to reference Quehenberger O, Armando AM, Brown AH, Milne SB, Myers DS, Merrill AH, et al. Lipidomics reveals a remarkable diversity of lipids in human plasma. J Lipid Res. 2010;51:3299–305.CrossRefPubMedPubMedCentral Quehenberger O, Armando AM, Brown AH, Milne SB, Myers DS, Merrill AH, et al. Lipidomics reveals a remarkable diversity of lipids in human plasma. J Lipid Res. 2010;51:3299–305.CrossRefPubMedPubMedCentral
26.
go back to reference Kanno K, Wu MK, Scapa EF, Roderick SL, Cohen DE. Structure and function of phosphatidylcholine transfer protein (PC-TP)/StarD2. Biochim Biophys Acta. 2007;1771:654–62.CrossRefPubMedPubMedCentral Kanno K, Wu MK, Scapa EF, Roderick SL, Cohen DE. Structure and function of phosphatidylcholine transfer protein (PC-TP)/StarD2. Biochim Biophys Acta. 2007;1771:654–62.CrossRefPubMedPubMedCentral
28.
go back to reference Lamari F, Mochel F, Sedel F, Saudubray JM. Disorders of phospholipids, sphingolipids and fatty acids biosynthesis: toward a new category of inherited metabolic diseases. J Inherit Metab Dis. 2013;36:411–25.CrossRefPubMed Lamari F, Mochel F, Sedel F, Saudubray JM. Disorders of phospholipids, sphingolipids and fatty acids biosynthesis: toward a new category of inherited metabolic diseases. J Inherit Metab Dis. 2013;36:411–25.CrossRefPubMed
29.
go back to reference Jakobsson A, Westerberg R, Jacobsson A. Fatty acid elongases in mammals: their regulation and roles in metabolism. Prog Lipid Res. 2006;45:237–49.CrossRefPubMed Jakobsson A, Westerberg R, Jacobsson A. Fatty acid elongases in mammals: their regulation and roles in metabolism. Prog Lipid Res. 2006;45:237–49.CrossRefPubMed
30.
go back to reference Gomase VS, Tagore S, Kale KV. Microarray: an approach for current drug targets. Curr Drug Metab. 2008;9:221–31.CrossRefPubMed Gomase VS, Tagore S, Kale KV. Microarray: an approach for current drug targets. Curr Drug Metab. 2008;9:221–31.CrossRefPubMed
31.
go back to reference Novak F, Tvrzicka E, Hamplova B, Kolar F, Novakova O. Postnatal development of phospholipids and their fatty acid profile in rat heart. Mol Cell Biochem. 2006;293:23–33.CrossRefPubMed Novak F, Tvrzicka E, Hamplova B, Kolar F, Novakova O. Postnatal development of phospholipids and their fatty acid profile in rat heart. Mol Cell Biochem. 2006;293:23–33.CrossRefPubMed
32.
go back to reference Slater-Jefferies JL, Hoile SP, Lillycrop KA, Townsend PA, Hanson MA, Burdge GC. Effect of sex and dietary fat intake on the fatty acid composition of phospholipids and triacylglycerol in rat heart. Prostaglandins Leukot Essent Fatty Acids. 2010;83:219–23.CrossRefPubMed Slater-Jefferies JL, Hoile SP, Lillycrop KA, Townsend PA, Hanson MA, Burdge GC. Effect of sex and dietary fat intake on the fatty acid composition of phospholipids and triacylglycerol in rat heart. Prostaglandins Leukot Essent Fatty Acids. 2010;83:219–23.CrossRefPubMed
33.
go back to reference Wahjudi PN, Yee JK, Martinez SR, Zhang J, Teitell M, Nikolaenko L, et al. Turnover of nonessential fatty acids in cardiolipin from the rat heart. J Lipid Res. 2011;52:2226–33.CrossRefPubMedPubMedCentral Wahjudi PN, Yee JK, Martinez SR, Zhang J, Teitell M, Nikolaenko L, et al. Turnover of nonessential fatty acids in cardiolipin from the rat heart. J Lipid Res. 2011;52:2226–33.CrossRefPubMedPubMedCentral
34.
go back to reference Jeckel KM, Miller KE, Chicco AJ, Chapman PL, Mulligan CM, Falcone PH, et al. The role of dietary fatty acids in predicting myocardial structure in fat-fed rats. Lipids in health and disease. 2011;10:92.CrossRefPubMedPubMedCentral Jeckel KM, Miller KE, Chicco AJ, Chapman PL, Mulligan CM, Falcone PH, et al. The role of dietary fatty acids in predicting myocardial structure in fat-fed rats. Lipids in health and disease. 2011;10:92.CrossRefPubMedPubMedCentral
35.
go back to reference Kien CL, Bunn JY, Poynter ME, Stevens R, Bain J, Ikayeva O, et al. A lipidomics analysis of the relationship between dietary fatty acid composition and insulin sensitivity in young adults. Diabetes. 2013;62:1054–63.CrossRefPubMedPubMedCentral Kien CL, Bunn JY, Poynter ME, Stevens R, Bain J, Ikayeva O, et al. A lipidomics analysis of the relationship between dietary fatty acid composition and insulin sensitivity in young adults. Diabetes. 2013;62:1054–63.CrossRefPubMedPubMedCentral
36.
go back to reference Shintu L, Baudoin R, Navratil V, Prot JM, Pontoizeau C, Defernez M, et al. Metabolomics-on-a-chip and predictive systems toxicology in microfluidic bioartificial organs. Anal Chem. 2012;84:1840–8.CrossRefPubMed Shintu L, Baudoin R, Navratil V, Prot JM, Pontoizeau C, Defernez M, et al. Metabolomics-on-a-chip and predictive systems toxicology in microfluidic bioartificial organs. Anal Chem. 2012;84:1840–8.CrossRefPubMed
37.
go back to reference Santos JL, Salemi VM, Picard MH, Mady C, Coelho OR. Subclinical regional left ventricular dysfunction in obese patients with and without hypertension or hypertrophy. Obesity. 2011;19:1296–303.CrossRefPubMed Santos JL, Salemi VM, Picard MH, Mady C, Coelho OR. Subclinical regional left ventricular dysfunction in obese patients with and without hypertension or hypertrophy. Obesity. 2011;19:1296–303.CrossRefPubMed
38.
go back to reference Ramirez E, Klett-Mingo M, Ares-Carrasco S, Picatoste B, Ferrarini A, Ruperez FJ, et al. Eplerenone attenuated cardiac steatosis, apoptosis and diastolic dysfunction in experimental type-II diabetes. Cardiovasc Diabetol. 2013;12:172.CrossRefPubMedPubMedCentral Ramirez E, Klett-Mingo M, Ares-Carrasco S, Picatoste B, Ferrarini A, Ruperez FJ, et al. Eplerenone attenuated cardiac steatosis, apoptosis and diastolic dysfunction in experimental type-II diabetes. Cardiovasc Diabetol. 2013;12:172.CrossRefPubMedPubMedCentral
39.
go back to reference Tepsic V, Ristic V, Ristic D, Vasiljevic N, Pecelj-Gec M. Heart phospholipid content and fatty acid composition in the rat after feeding different lipid supplemented diets. Physiol Res Acad Sci Bohemoslov. 1998;47:413–8. Tepsic V, Ristic V, Ristic D, Vasiljevic N, Pecelj-Gec M. Heart phospholipid content and fatty acid composition in the rat after feeding different lipid supplemented diets. Physiol Res Acad Sci Bohemoslov. 1998;47:413–8.
40.
go back to reference Van de Velde M, DeWolff M, Leather HA, Wouters PF. Effects of lipids on the functional and metabolic recovery from global myocardial stunning in isolated rabbit hearts. Cardiovasc Res. 2000;48:129–37.CrossRefPubMed Van de Velde M, DeWolff M, Leather HA, Wouters PF. Effects of lipids on the functional and metabolic recovery from global myocardial stunning in isolated rabbit hearts. Cardiovasc Res. 2000;48:129–37.CrossRefPubMed
41.
go back to reference Demarco VG, Ford DA, Henriksen EJ, Aroor AR, Johnson MS, Habibi J, et al. Obesity-related alterations in cardiac lipid profile and nondipping blood pressure pattern during transition to diastolic dysfunction in male db/db mice. Endocrinology. 2013;154:159–71.CrossRefPubMed Demarco VG, Ford DA, Henriksen EJ, Aroor AR, Johnson MS, Habibi J, et al. Obesity-related alterations in cardiac lipid profile and nondipping blood pressure pattern during transition to diastolic dysfunction in male db/db mice. Endocrinology. 2013;154:159–71.CrossRefPubMed
Metadata
Title
Changes of myocardial lipidomics profiling in a rat model of diabetic cardiomyopathy using UPLC/Q-TOF/MS analysis
Authors
Shifen Dong
Rong Zhang
Yaoyue Liang
Jiachen Shi
Jiajia Li
Fei Shang
Xuezhou Mao
Jianning Sun
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Diabetology & Metabolic Syndrome / Issue 1/2017
Electronic ISSN: 1758-5996
DOI
https://doi.org/10.1186/s13098-017-0249-6

Other articles of this Issue 1/2017

Diabetology & Metabolic Syndrome 1/2017 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.