Subscribe to RSS

DOI: 10.1055/a-1693-8356
Effects of Lipid Overload on Heart in Metabolic Diseases
Funding Information This work was supported by Tianjin Postgraduate Research and Innovation Project (2020YJSB196).
Abstract
Metabolic diseases are often associated with lipid and glucose metabolism abnormalities, which increase the risk of cardiovascular disease. Diabetic cardiomyopathy (DCM) is an important development of metabolic diseases and a major cause of death. Lipids are the main fuel for energy metabolism in the heart. The increase of circulating lipids affects the uptake and utilization of fatty acids and glucose in the heart, and also affects mitochondrial function. In this paper, the mechanism of lipid overload in metabolic diseases leading to cardiac energy metabolism disorder is discussed.
Key words
lipid metabolism - cardiac energy metabolism - metabolic diseases - metabolic syndrome - type 2 diabetes - diabetic cardiomyopathyPublication History
Received: 16 August 2021
Accepted after revision: 29 October 2021
Article published online:
10 December 2021
© 2021. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)
Georg Thieme Verlag
Rüdigerstraße 14, 70469 Stuttgart,
Germany
-
References
- 1 Faramawi MF, Delhey L, Abouelenein S. et al Metabolic syndrome and P-wave duration in the American population. Ann Epidemiol 2020; 46: 5-11
- 2 Welsh C, Welsh P, Celis-Morales CA. et al Glycated hemoglobin, prediabetes, and the links to cardiovascular disease: data From UK biobank. Diabetes Care 2020; 43: 440-445
- 3 Spence JD, Viscoli CM, Inzucchi SE. et al Pioglitazone therapy in patients with stroke and prediabetes: a post hoc analysis of the IRIS randomized clinical trial. JAMA Neurol 2019; 76: 526-535
- 4 Sorensen BM, Houben AJ, Berendschot TT. et al Prediabetes and type 2 diabetes are associated with generalized microvascular dysfunction: the Maastricht study. Circulation 2016; 134: 1339-1352
- 5 Rhee EJ, Kwon H, Park SE. et al Associations among obesity degree, glycemic status, and risk of heart failure in 9,720,220 Korean adults. Diabetes Metab J 2020; 44: 592-601
- 6 Linssen PBC, Veugen MGJ, Henry RMA. et al Associations of (pre)diabetes with right ventricular and atrial structure and function: the Maastricht Study. Cardiovasc Diabetol 2020; 19: 88
- 7 Kristensen SL, Preiss D, Jhund PS. et al. Risk related to pre-diabetes mellitus and diabetes mellitus in heart failure with reduced ejection fraction: insights from prospective comparison of ARNI with ACEI to determine impact on global mortality and morbidity in heart failure trial. Circ Heart Fail. 2016 9.
- 8 Selvin E, Lazo M, Chen Y. et al Diabetes mellitus, prediabetes, and incidence of subclinical myocardial damage. Circulation 2014; 130: 1374-1382
- 9 Burchfiel CM, Skelton TN, Andrew ME. et al Metabolic syndrome and echocardiographic left ventricular mass in blacks: the atherosclerosis risk in communities (ARIC) study. Circulation 2005; 112: 819-827
- 10 Fontes-Carvalho R, Ladeiras-Lopes R, Bettencourt P. et al Diastolic dysfunction in the diabetic continuum: association with insulin resistance, metabolic syndrome and type 2 diabetes. Cardiovasc Diabetol 2015; 14: 4
- 11 Jia G, Whaley-Connell A, Sowers JR. Diabetic cardiomyopathy: a hyperglycaemia- and insulin-resistance-induced heart disease. Diabetologia 2018; 61: 21-28
- 12 Dillmann WH. Diabetic cardiomyopathy. Circ Res 2019; 124: 1160-1162
- 13 Federico M, De la Fuente S, Palomeque J. et al The role of mitochondria in metabolic disease: a special emphasis on heart dysfunction. J Physiol 2021; 599: 3477-3493
- 14 Gao Y, Ren Y, Guo YK. et al Metabolic syndrome and myocardium steatosis in subclinical type 2 diabetes mellitus: a (1)H-magnetic resonance spectroscopy study. Cardiovasc Diabetol 2020; 19: 70
- 15 Marfella R, Di Filippo C, Portoghese M. et al Myocardial lipid accumulation in patients with pressure-overloaded heart and metabolic syndrome. J Lipid Res 2009; 50: 2314-2323
- 16 Costantino S, Akhmedov A, Melina G. et al Obesity-induced activation of JunD promotes myocardial lipid accumulation and metabolic cardiomyopathy. Eur Heart J 2019; 40: 997-1008
- 17 Doenst T, Nguyen TD, Abel ED. Cardiac metabolism in heart failure: implications beyond ATP production. Circ Res 2013; 113: 709-724
- 18 Horikoshi Y, Yan Y, Terashvili M. et al Fatty acid-treated induced pluripotent stem cell-derived human cardiomyocytes exhibit adult cardiomyocyte-like energy metabolism phenotypes. Cells. 2019 8.
- 19 Bekhite MM, Gonzalez Delgado A, Menz F. et al Longitudinal metabolic profiling of cardiomyocytes derived from human-induced pluripotent stem cells. Basic Res Cardiol 2020; 115: 37
- 20 Dolinsky VW, Dyck JR. Role of AMP-activated protein kinase in healthy and diseased hearts. Am J Physiol Heart Circ Physiol 2006; 291: H2557-H2569
- 21 Neubauer S. The failing heart--an engine out of fuel. N Engl J Med 2007; 356: 1140-1151
- 22 Luiken J, Nabben M, Neumann D. et al Understanding the distinct subcellular trafficking of CD36 and GLUT4 during the development of myocardial insulin resistance. Biochim Biophys Acta Mol Basis Dis 2020; 1866: 165775
- 23 Kerr M, Dodd MS, Heather LC. The ‘Goldilocks zone’ of fatty acid metabolism; to ensure that the relationship with cardiac function is just right. Clin Sci (Lond) 2017; 131: 2079-2094
- 24 Lopaschuk GD, Ussher JR, Folmes CD. et al Myocardial fatty acid metabolism in health and disease. Physiol Rev 2010; 90: 207-258
- 25 McGarry JD, Mannaerts GP, Foster DW. A possible role for malonyl-CoA in the regulation of hepatic fatty acid oxidation and ketogenesis. J Clin Invest 1977; 60: 265-270
- 26 Priesnitz C, Becker T. Pathways to balance mitochondrial translation and protein import. Genes Dev 2018; 32: 1285-1296
- 27 Caruana NJ, Stroud DA. The road to the structure of the mitochondrial respiratory chain supercomplex. Biochem Soc Trans 2020; 48: 621-629
- 28 Mehdipour AR, Hummer G. Cardiolipin puts the seal on ATP synthase. Proc Natl Acad Sci U S A 2016; 113: 8568-8570
- 29 Zhu B, Li MY, Lin Q. et al Lipid oversupply induces CD36 sarcolemmal translocation via dual modulation of PKCzeta and TBC1D1: an early event prior to insulin resistance. Theranostics 2020; 10: 1332-1354
- 30 Glatz JF, Luiken JJ. From fat to FAT (CD36/SR-B2): Understanding the regulation of cellular fatty acid uptake. Biochimie 2017; 136: 21-26
- 31 Ouwens DM, Diamant M, Fodor M. et al Cardiac contractile dysfunction in insulin-resistant rats fed a high-fat diet is associated with elevated CD36-mediated fatty acid uptake and esterification. Diabetologia 2007; 50: 1938-1948
- 32 Angin Y, Steinbusch LK, Simons PJ. et al CD36 inhibition prevents lipid accumulation and contractile dysfunction in rat cardiomyocytes. Biochem J 2012; 448: 43-53
- 33 Bonen A, Jain SS, Snook LA. et al Extremely rapid increase in fatty acid transport and intramyocellular lipid accumulation but markedly delayed insulin resistance after high fat feeding in rats. Diabetologia 2015; 58: 2381-2391
- 34 Renguet E, Bultot L, Beauloye C. et al The regulation of insulin-stimulated cardiac glucose transport via protein acetylation. Front Cardiovasc Med 2018; 5: 70
- 35 Chaurasia B, Tippetts TS, Mayoral Monibas R. et al Targeting a ceramide double bond improves insulin resistance and hepatic steatosis. Science 2019; 365: 386-392
- 36 Zhang L, Ussher JR, Oka T. et al Cardiac diacylglycerol accumulation in high fat-fed mice is associated with impaired insulin-stimulated glucose oxidation. Cardiovasc Res 2011; 89: 148-156
- 37 Sung MM, Byrne NJ, Kim TT. et al Cardiomyocyte-specific ablation of CD36 accelerates the progression from compensated cardiac hypertrophy to heart failure. Am J Physiol Heart Circ Physiol 2017; 312: H552-H560
- 38 Glatz JFC, Nabben M, Young ME. et al Re-balancing cellular energy substrate metabolism to mend the failing heart. Biochim Biophys Acta Mol Basis Dis 2020; 1866: 165579
- 39 Wang S, Schianchi F, Neumann D. et al Specific amino acid supplementation rescues the heart from lipid overload-induced insulin resistance and contractile dysfunction by targeting the endosomal mTOR-v-ATPase axis. Mol Metab 2021; 53: 101293
- 40 Kim G, Jo K, Kim KJ. et al Visceral adiposity is associated with altered myocardial glucose uptake measured by (18)FDG-PET in 346 subjects with normal glucose tolerance, prediabetes, and type 2 diabetes. Cardiovasc Diabetol 2015; 14: 148
- 41 Cortassa S, Caceres V, Tocchetti CG. et al Metabolic remodelling of glucose, fatty acid and redox pathways in the heart of type 2 diabetic mice. J Physiol 2020; 598: 1393-1415
- 42 Belke DD, Larsen TS, Gibbs EM. et al Altered metabolism causes cardiac dysfunction in perfused hearts from diabetic (db/db) mice. Am J Physiol Endocrinol Metab 2000; 279: E1104-E1113
- 43 Fukushima A, Lopaschuk GD. Cardiac fatty acid oxidation in heart failure associated with obesity and diabetes. Biochim Biophys Acta 2016; 1861: 1525-1534
- 44 Carpentier AC. Abnormal myocardial dietary fatty acid metabolism and diabetic cardiomyopathy. Can J Cardiol 2018; 34: 605-614
- 45 Cole MA, Murray AJ, Cochlin LE. et al A high fat diet increases mitochondrial fatty acid oxidation and uncoupling to decrease efficiency in rat heart. Basic Res Cardiol 2011; 106: 447-457
- 46 Finck BN, Lehman JJ, Leone TC. et al The cardiac phenotype induced by PPARalpha overexpression mimics that caused by diabetes mellitus. J Clin Invest 2002; 109: 121-130
- 47 Dyck JR, Cheng JF, Stanley WC. et al Malonyl coenzyme a decarboxylase inhibition protects the ischemic heart by inhibiting fatty acid oxidation and stimulating glucose oxidation. Circ Res 2004; 94: e78-e84
- 48 Donelson J, Wang Q, Monroe TO. et al Cardiac-specific ablation of glutaredoxin 3 leads to cardiac hypertrophy and heart failure. Physiol Rep 2019; 7: e14071
- 49 Lillig CH, Berndt C, Holmgren A. Glutaredoxin systems. Biochim Biophys Acta 2008; 1780: 1304-1317
- 50 Cheng N, Mo Q, Donelson J. et al Crucial role of mammalian glutaredoxin 3 in cardiac energy metabolism in diet-induced obese mice revealed by transcriptome analysis. Int J Biol Sci 2021; 17: 2871-2883
- 51 Ying F, Liu H, Ching Tang EH. et al Prostaglandin E receptor subtype 4 protects against diabetic cardiomyopathy by modulating cardiac fatty acid metabolism via FOXO1/CD36 signalling. Biochem Biophys Res Commun 2021; 548: 196-203
- 52 Mishra P, Chan DC. Metabolic regulation of mitochondrial dynamics. J Cell Biol 2016; 212: 379-387
- 53 Koncsos G, Varga ZV, Baranyai T. et al Diastolic dysfunction in prediabetic male rats: Role of mitochondrial oxidative stress. Am J Physiol Heart Circ Physiol 2016; 311: H927-H943
- 54 Sverdlov AL, Elezaby A, Qin F. et al Mitochondrial reactive oxygen species mediate cardiac structural, functional, and mitochondrial consequences of diet-induced metabolic heart disease. J Am Heart Assoc. 2016 5.
- 55 Boudina S, Sena S, Theobald H. et al Mitochondrial energetics in the heart in obesity-related diabetes: direct evidence for increased uncoupled respiration and activation of uncoupling proteins. Diabetes 2007; 56: 2457-2466
- 56 Boudina S, Bugger H, Sena S. et al Contribution of impaired myocardial insulin signaling to mitochondrial dysfunction and oxidative stress in the heart. Circulation 2009; 119: 1272-1283
- 57 Belke DD, Betuing S, Tuttle MJ. et al Insulin signaling coordinately regulates cardiac size, metabolism, and contractile protein isoform expression. J Clin Invest 2002; 109: 629-639
- 58 Maneechote C, Palee S, Apaijai N. et al Mitochondrial dynamic modulation exerts cardiometabolic protection in obese insulin-resistant rats. Clin Sci (Lond) 2019; 133: 2431-2447
- 59 Waddingham MT, Sonobe T, Tsuchimochi H. et al Diastolic dysfunction is initiated by cardiomyocyte impairment ahead of endothelial dysfunction due to increased oxidative stress and inflammation in an experimental prediabetes model. J Mol Cell Cardiol 2019; 137: 119-131
- 60 Stacchiotti A, Favero G, Giugno L. et al Melatonin efficacy in obese leptin-deficient mice heart. Nutrients. 2017 9.
- 61 Gottlieb RA, Gustafsson AB. Mitochondrial turnover in the heart. Biochim Biophys Acta 2011; 1813: 1295-1301
- 62 Gao S, Hu J. Mitochondrial fusion: the machineries in and out. Trends Cell Biol 2021; 31: 62-74
- 63 Filadi R, Pendin D, Pizzo P. Mitofusin 2: from functions to disease. Cell Death Dis 2018; 9: 330
- 64 Tezze C, Romanello V, Desbats MA. et al Age-associated loss of OPA1 in muscle impacts muscle mass, metabolic homeostasis, systemic inflammation, and epithelial senescence. Cell Metab 2017; 25: 1374-1389 e1376
- 65 Elezaby A, Sverdlov AL, Tu VH. et al Mitochondrial remodeling in mice with cardiomyocyte-specific lipid overload. J Mol Cell Cardiol 2015; 79: 275-283
- 66 Hu Q, Zhang H, Gutierrez Cortes N. et al Increased Drp1 acetylation by lipid overload induces cardiomyocyte death and heart dysfunction. Circ Res 2020; 126: 456-470
- 67 Tsushima K, Bugger H, Wende AR. et al Mitochondrial reactive oxygen species in lipotoxic hearts induce post-translational modifications of AKAP121, DRP1, and OPA1 that promote mitochondrial fission. Circ Res 2018; 122: 58-73
- 68 Schaffer JE. Lipotoxicity: when tissues overeat. Curr Opin Lipidol 2003; 14: 281-287
- 69 Nakamura M, Liu T, Husain S. et al Glycogen synthase kinase-3alpha promotes fatty acid uptake and lipotoxic cardiomyopathy. Cell Metab 2019; 29: 1119-1134 e1112
- 70 Roe ND, Handzlik MK, Li T. et al The role of diacylglycerol acyltransferase (DGAT) 1 and 2 in cardiac metabolism and function. Sci Rep 2018; 8: 4983
- 71 Peterson LR, Xanthakis V, Duncan MS. et al Ceramide remodeling and risk of cardiovascular events and mortality. J Am Heart Assoc. 2018 7.
- 72 Ljubkovic M, Gressette M, Bulat C. et al Disturbed fatty acid oxidation, endoplasmic reticulum stress, and apoptosis in left ventricle of patients with type 2 diabetes. Diabetes 2019; 68: 1924-1933
- 73 de la Monte SM, Tong M, Nguyen V. et al Ceramide-mediated insulin resistance and impairment of cognitive-motor functions. J Alzheimers Dis 2010; 21: 967-984
- 74 Summers SA, Chaurasia B, Holland WL. Metabolic messengers: ceramides. Nat Metab 2019; 1: 1051-1058
- 75 Blair HC, Sepulveda J, Papachristou DJ. Nature and nurture in atherosclerosis: the roles of acylcarnitine and cell membrane-fatty acid intermediates. Vascul Pharmacol 2016; 78: 17-23
- 76 Pande SV, Blanchaer MC. Reversible inhibition of mitochondrial adenosine diphosphate phosphorylation by long chain acyl coenzyme A esters. J Biol Chem 1971; 246: 402-411
- 77 Ciapaite J, Van Eikenhorst G, Bakker SJ. et al Modular kinetic analysis of the adenine nucleotide translocator-mediated effects of palmitoyl-CoA on the oxidative phosphorylation in isolated rat liver mitochondria. Diabetes 2005; 54: 944-951
- 78 Kerr M, Dennis K, Carr CA. et al Diabetic mitochondria are resistant to palmitoyl CoA inhibition of respiration, which is detrimental during ischemia. FASEB J 2021; 35: e21765
- 79 Schianchi F, Glatz JFC, Navarro Gascon A. et al Putative role of protein palmitoylation in cardiac lipid-induced insulin resistance. Int J Mol Sci. 2020 21.
- 80 Dasgupta S, Bhattacharya S, Maitra S. et al Mechanism of lipid induced insulin resistance: activated PKCepsilon is a key regulator. Biochim Biophys Acta 2011; 1812: 495-506
- 81 Zhao L, Zhang C, Luo X. et al CD36 palmitoylation disrupts free fatty acid metabolism and promotes tissue inflammation in non-alcoholic steatohepatitis. J Hepatol 2018; 69: 705-717
- 82 Sundaresan NR, Pillai VB, Wolfgeher D. et al The deacetylase SIRT1 promotes membrane localization and activation of Akt and PDK1 during tumorigenesis and cardiac hypertrophy. Sci Signal 2011; 4: ra46
- 83 Alrob OA, Sankaralingam S, Ma C. et al Obesity-induced lysine acetylation increases cardiac fatty acid oxidation and impairs insulin signalling. Cardiovasc Res 2014; 103: 485-497
- 84 Aurigemma GP, de Simone G, Fitzgibbons TP. Cardiac remodeling in obesity. Circ Cardiovasc Imaging 2013; 6: 142-152
- 85 Apaijai N, Arinno A, Palee S. et al High-saturated fat high-sugar diet accelerates left-ventricular dysfunction faster than high-saturated fat diet alone via increasing oxidative stress and apoptosis in obese-insulin resistant rats. Mol Nutr Food Res 2019; 63: e1800729
- 86 Han L, Liu J, Zhu L. et al Free fatty acid can induce cardiac dysfunction and alter insulin signaling pathways in the heart. Lipids Health Dis 2018; 17: 185
- 87 Wang Z, Wang Y, Han Y. et al Akt is a critical node of acute myocardial insulin resistance and cardiac dysfunction after cardiopulmonary bypass. Life Sci 2019; 234: 116734
- 88 Bockus LB, Matsuzaki S, Vadvalkar SS. et al Cardiac insulin signaling regulates glycolysis through phosphofructokinase 2 content and activity. J Am Heart Assoc. 2017 6.
- 89 Gejl M, Sondergaard HM, Stecher C. et al Exenatide alters myocardial glucose transport and uptake depending on insulin resistance and increases myocardial blood flow in patients with type 2 diabetes. J Clin Endocrinol Metab 2012; 97: E1165-E1169
- 90 Sondergaard HM, Bottcher M, Marie Madsen M. et al Impact of type 2 diabetes on myocardial insulin sensitivity to glucose uptake and perfusion in patients with coronary artery disease. J Clin Endocrinol Metab 2006; 91: 4854-4861
- 91 Yu C, Chen Y, Cline GW. et al Mechanism by which fatty acids inhibit insulin activation of insulin receptor substrate-1 (IRS-1)-associated phosphatidylinositol 3-kinase activity in muscle. J Biol Chem 2002; 277: 50230-50236
- 92 Wali JA, Jarzebska N, Raubenheimer D. et al Cardio-metabolic effects of high-fat diets and their underlying mechanisms - a narrative review. Nutrients. 2020 12.
- 93 Summers SA, Garza LA, Zhou H. et al Regulation of insulin-stimulated glucose transporter GLUT4 translocation and Akt kinase activity by ceramide. Mol Cell Biol 1998; 18: 5457-5464
- 94 Chen TC, Benjamin DI, Kuo T. et al The glucocorticoid-Angptl4-ceramide axis induces insulin resistance through PP2A and PKCzeta. Sci Signal. 2017 10.
- 95 Uddin GM, Zhang L, Shah S. et al Impaired branched chain amino acid oxidation contributes to cardiac insulin resistance in heart failure. Cardiovasc Diabetol 2019; 18: 86
- 96 Sung HK, Song E, Jahng JWS. et al Iron induces insulin resistance in cardiomyocytes via regulation of oxidative stress. Sci Rep 2019; 9: 4668
- 97 Neinast MD, Jang C, Hui S. et al Quantitative analysis of the whole-body metabolic fate of branched-chain amino acids. Cell Metab 2019; 29: 417-429 e414
- 98 Lantier L, Williams AS, Williams IM. et al Reciprocity between skeletal muscle AMPK deletion and insulin action in diet-induced obese mice. Diabetes 2020; 69: 1636-1649
- 99 Ke R, Xu Q, Li C. et al Mechanisms of AMPK in the maintenance of ATP balance during energy metabolism. Cell Biol Int 2018; 42: 384-392