Metabolic and Biochemical Stressors in Diabetic Cardiomyopathy

Diabetic cardiomyopathy (DCM) or diabetes-induced cardiac dysfunction is a direct consequence of uncontrolled metabolic syndrome and is widespread in US population and worldwide. Despite of the heterogeneous and distinct features of DCM, the clinical relevance of DCM is now becoming established. DCM progresses to pathological cardiac remodeling with the higher risk of heart attack and subsequent heart failure in diabetic patients. In this review, we emphasize lipid substrate quality and the phenotypic, metabolic, and biochemical stressors of DCM in the rodent and human pathophysiology. We discuss lipoxygenase signaling in the inflammatory pathway with multiple contributing and confounding factors leading to DCM. Additionally, emerging biochemical pathways are emphasized to make progress toward therapeutic advancement to treat DCM.

• Publication year

  2017

• Venue

  Frontiers in Cardiovascular Medicine

• Publication date

  2017-05-31

• Fields of study

  Biology, Medicine, Environmental Science

• Identifiers
  DOI 10.3389/fcvm.2017.00031PMID 28620607PMCID 5449449
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Adipose tissue plasticity: how fat depots respond differently to pathophysiological cues

  2016cited by this paper
• High glucose facilitated endothelial heparanase transfer to the cardiomyocyte modifies its cell death signature.

  2016cited by this paper
• A targeted metabolomics assay for cardiac metabolism and demonstration using a mouse model of dilated cardiomyopathy

  2016cited by this paper
• Aging dysregulates D- and E-series resolvins to modulate cardiosplenic and cardiorenal network following myocardial infarction

  2016cited by this paper
• Uric Acid Promotes Left Ventricular Diastolic Dysfunction in Mice Fed a Western Diet

  2015cited by this paper
• Obesity superimposed on aging magnifies inflammation and delays the resolving response after myocardial infarction.

  2015cited by this paper
• Association between 7 years of intensive treatment of type 1 diabetes and long-term mortality.

  2015cited by this paper
• Cardiomyocyte-specific Bmal1 deletion in mice triggers diastolic dysfunction, extracellular matrix response, and impaired resolution of inflammation.

  2015cited by this paper
• Severe hypoglycemia and coronary artery calcification during the diabetes control and complications trial/epidemiology of diabetes interventions and complications (DCCT/EDIC) study.

  2015cited by this paper
• Prospective association of fatty acids in the de novo lipogenesis pathway with risk of type 2 diabetes: the Cardiovascular Health Study.

  2015influential reference
• Personalized Nutrition by Prediction of Glycemic Responses.

  2015cited by this paper
• Metabolic Syndrome is Associated With Higher Wall Motion Score and Larger Infarct Size After Acute Myocardial Infarction

  2015cited by this paper
• The role of cardiac lipotoxicity in the pathogenesis of diabetic cardiomyopathy

  2014cited by this paper
• Cardiovascular impact of drugs used in the treatment of diabetes

  2014cited by this paper
• Arachidonate 12/15-Lipoxygenase–Induced Inflammation and Oxidative Stress Are Involved in the Development of Diabetic Cardiomyopathy

  2014influential reference
• Cardiac-specific adipose triglyceride lipase overexpression protects from cardiac steatosis and dilated cardiomyopathy following diet-induced obesity

  2014cited by this paper
• Cardiomyocyte-Specific BMAL1 Plays Critical Roles in Metabolism, Signaling, and Maintenance of Contractile Function of the Heart

  2014cited by this paper
• Mitochondrial fatty acid oxidation alterations in heart failure, ischaemic heart disease and diabetic cardiomyopathy

  2014cited by this paper
• 12-Lipoxygenase Promotes Obesity-Induced Oxidative Stress in Pancreatic Islets

  2014cited by this paper
• Diabetes as a risk factor for stroke in women compared with men: a systematic review and meta-analysis of 64 cohorts, including 775,385 individuals and 12,539 strokes.

  2014cited by this paper
• Cardiac-specific ablation of ARNT leads to lipotoxicity and cardiomyopathy.

  2014cited by this paper
• Angiotensin 1–7 Ameliorates Diabetic Cardiomyopathy and Diastolic Dysfunction in db/db Mice by Reducing Lipotoxicity and Inflammation

  2014cited by this paper
• Flaxseed Consumption Reduces Blood Pressure in Patients With Hypertension by Altering Circulating Oxylipins via an &agr;-Linolenic Acid–Induced Inhibition of Soluble Epoxide Hydrolase

  2014cited by this paper
• Prevalence of childhood and adult obesity in the United States, 2011-2012.

  2014cited by this paper
• Dissecting the Mechanisms of Left Ventricular Diastolic Dysfunction and Inflammation in Peritoneal Dialysis Patients

  2013cited by this paper
• Therapeutic effect of MG-132 on diabetic cardiomyopathy is associated with its suppression of proteasomal activities: roles of Nrf2 and NF-κB.

  2013cited by this paper
• Human inflammatory and resolving lipid mediator responses to resistance exercise and ibuprofen treatment.

  2013cited by this paper
• Obesity resistance and deregulation of lipogenesis in Δ6‐fatty acid desaturase (FADS2) deficiency

  2013cited by this paper
• Targeted analysis of omega‐6‐derived eicosanoids in human serum by SPE‐LC‐MS/MS for evaluation of coronary artery disease

  2013cited by this paper
• Delta-6-desaturase Links Polyunsaturated Fatty Acid Metabolism With Phospholipid Remodeling and Disease Progression in Heart Failure

  2013cited by this paper
• Diabetes and the Heart: Is There Objective Evidence of a Human Diabetic Cardiomyopathy?

  2013influential reference
• Impact of obesity and the obesity paradox on prevalence and prognosis in heart failure.

  2013cited by this paper
• Metformin: an old but still the best treatment for type 2 diabetes

  2013cited by this paper
• Balancing the fat: lipid droplets and human disease

  2013cited by this paper
• Diets rich in n-6 PUFA induce intestinal microbial dysbiosis in aged mice

  2013cited by this paper
• Cardiac metabolism and its interactions with contraction, growth, and survival of cardiomyocytes.

  2013cited by this paper
• 20-Hydroxyeicosatetraenoic acid is a potential therapeutic target in cardiovascular diseases.

  2013influential reference
• High Fat Feeding in Mice Is Insufficient to Induce Cardiac Dysfunction and Does Not Exacerbate Heart Failure

  2013cited by this paper
• Diabetic cardiomyopathy and metabolic remodeling of the heart.

  2013cited by this paper
• Short‐Term Lenalidomide (Revlimid) Administration Ameliorates Cardiomyocyte Contractile Dysfunction in ob/ob Obese Mice

  2012cited by this paper
• TLR4 regulates cardiac lipid accumulation and diabetic heart disease in the nonobese diabetic mouse model of type 1 diabetes.

  2012cited by this paper
• Linking placental ischemia and hypertension in preeclampsia: role of endothelin 1.

  2012cited by this paper
• Mice lacking macrophage 12/15-lipoxygenase are resistant to experimental hypertension.

  2012cited by this paper
• Obesity-mediated inflammatory microenvironment stimulates osteoclastogenesis and bone loss in mice.

  2011cited by this paper
• Potential Role of Nuclear Factor κB in Diabetic Cardiomyopathy

  2011cited by this paper
• Heart in Diabetes: A Microvascular Disease

  2011cited by this paper
• Improvement of Cardiac Functions by Chronic Metformin Treatment Is Associated With Enhanced Cardiac Autophagy in Diabetic OVE26 Mice

  2011cited by this paper
• Disruption of Circadian Rhythms Accelerates Development of Diabetes through Pancreatic Beta-Cell Loss and Dysfunction

  2011cited by this paper
• Targeted Inhibition of Calpain Reduces Myocardial Hypertrophy and Fibrosis in Mouse Models of Type 1 Diabetes

  2011cited by this paper
• Effect of diabetes and hypertension on left ventricular diastolic function in a high‐risk population without evidence of heart disease

  2010cited by this paper
• Diabetes reduces the cholesterol exporter ABCA1 in mouse macrophages and kidneys1

  2010cited by this paper
• Gender differences in coronary heart disease

  2010cited by this paper
• High fat diet-induced animal model of age-associated obesity and osteoporosis.

  2010cited by this paper
• Lipotoxicity in the heart.

  2010cited by this paper
• FoxO, Autophagy, and Cardiac Remodeling

  2010cited by this paper
• Naturally occurring monoepoxides of eicosapentaenoic acid and docosahexaenoic acid are bioactive antihyperalgesic lipids[S]

  2010influential reference
• Modulation of myocardial metabolism: an emerging therapeutic principle

  2010cited by this paper
• Effect of a High Intake of Conjugated Linoleic Acid on Lipoprotein Levels in Healthy Human Subjects

  2010cited by this paper
• Diabetic cardiomyopathy: from the pathophysiology of the cardiac myocytes to current diagnosis and management strategies

  2010cited by this paper
• Diabetic Cardiomyopathy: Mechanisms and Therapeutic Targets.

  2010cited by this paper
• Cardiac and renal function are progressively impaired with aging in Zucker diabetic fatty type II diabetic rats

  2009cited by this paper
• Heart Disease and Stroke Statistics—2015 Update: A Report From the American Heart Association

  2009influential reference
• Rac1 Is Required for Cardiomyocyte Apoptosis During Hyperglycemia

  2009cited by this paper
• Correlation Relationship Assessment between Left Ventricular Hypertrophy Voltage Criteria and Body Mass Index in 41,806 Swiss Conscripts

  2009influential reference
• Recent progress in the biology and physiology of sirtuins

  2009cited by this paper
• Myocardial fibrosis and apoptosis, but not inflammation, are present in long-term experimental diabetes.

  2009cited by this paper
• 10-year follow-up of diabetes incidence and weight loss in the Diabetes Prevention Program Outcomes Study.

  2009cited by this paper
• Cardiac 12/15 lipoxygenase–induced inflammation is involved in heart failure

  2009cited by this paper
• Dyslipidaemia in type II diabetic mice does not aggravate contractile impairment but increases ventricular stiffness.

  2008cited by this paper
• Cardiac remodeling in obesity.

  2008cited by this paper
• Genetics Meets Metabolomics: A Genome-Wide Association Study of Metabolite Profiles in Human Serum

  2008cited by this paper
• Hypertension in Response to Chronic Reductions in Uterine Perfusion in Pregnant Rats: Effect of Tumor Necrosis Factor-&agr; Blockade

  2008cited by this paper
• Association between diabetes mellitus and left ventricular hypertrophy in a multiethnic population.

  2008cited by this paper
• 14-3-3 protein regulates Ask1 signaling and protects against diabetic cardiomyopathy.

  2008cited by this paper
• Δ6‐Desaturase (FADS2) deficiency unveils the role of ω3‐ and ω6‐polyunsaturated fatty acids

  2008cited by this paper
• Role of endothelin‐1, sodium hydrogen exchanger‐1 and mitogen activated protein kinase (MAPK) activation in glucose‐induced cardiomyocyte hypertrophy

  2007cited by this paper
• Diabetic Cardiomyopathy in OVE26 Mice Shows Mitochondrial ROS Production and Divergence Between In Vivo and In Vitro Contractility.

  2007cited by this paper
• Tumor necrosis factor-alpha induces insulin resistance in endothelial cells via a p38 mitogen-activated protein kinase-dependent pathway.

  2007cited by this paper
• FoxO transcription factors activate Akt and attenuate insulin signaling in heart by inhibiting protein phosphatases

  2007cited by this paper
• Mitochondrial Energetics in the Heart in Obesity-Related Diabetes

  2007cited by this paper
• Tumor Necrosis Factor- (cid:1) Induces Insulin Resistance in Endothelial Cells via a p38 Mitogen-Activated Protein Kinase-Dependent Pathway

  2007cited by this paper
• Magnetic resonance imaging of progressive cardiomyopathic changes in the db/db mouse.

  2007cited by this paper
• Cardiomyocyte dysfunction in models of type 1 and type 2 diabetes

  2007cited by this paper
• PPARs and their metabolic modulation: new mechanisms for transcriptional regulation?

  2007cited by this paper
• Clinical epidemiology of heart failure

  2007cited by this paper
• Role of protein O-linked N-acetyl-glucosamine in mediating cell function and survival in the cardiovascular system.

  2007cited by this paper
• Cardiac Steatosis in Diabetes Mellitus: A 1H-Magnetic Resonance Spectroscopy Study

  2007cited by this paper
• CONVERGENCE OF GLUCOSE‐ AND FATTY ACID‐INDUCED ABNORMAL MYOCARDIAL EXCITATION–CONTRACTION COUPLING AND INSULIN SIGNALLING

  2006cited by this paper
• Gene therapy for diabetic cardiomyopathy: a new approach for a difficult problem.

  2006cited by this paper
• Left ventricular dysfunction and remodeling in streptozotocin-induced diabetic rats.

  2006cited by this paper
• Foxo Transcription Factors Blunt Cardiac Hypertrophy by Inhibiting Calcineurin Signaling

  2006cited by this paper
• The pathogenesis of myocardial fibrosis in the setting of diabetic cardiomyopathy.

  2006cited by this paper
• Fatty Acids Attenuate Insulin Regulation of 5′-AMP–Activated Protein Kinase and Insulin Cardioprotection After Ischemia

  2006cited by this paper
• Blockade of the Renin–Angiotensin System Attenuates Sarcolemma and Sarcoplasmic Reticulum Remodeling in Chronic Diabetes

  2006cited by this paper
• Cardiomyocyte apoptosis induced by short-term diabetes requires mitochondrial GSH depletion.

  2005cited by this paper
• The Population-Based Acute Myocardial Infarction (AMI) Registry of the MONICA/KORA Study Region of Augsburg

  2005cited by this paper
• The NOD mouse: a model of immune dysregulation.

  2005cited by this paper
• Insulin Resistance and Congestive Heart Failure--Reply

  2005cited by this paper
• Reduced Mitochondrial Oxidative Capacity and Increased Mitochondrial Uncoupling Impair Myocardial Energetics in Obesity

  2005cited by this paper
• Reduced cardiac efficiency and altered substrate metabolism precedes the onset of hyperglycemia and contractile dysfunction in two mouse models of insulin resistance and obesity.

  2005cited by this paper

• Morin protects against palmitic acid-induced diabetic cardiomyopathy via SIRT6 activation and mitochondrial preservation

  2025cites this paper
• Skin manifestations in diabetes—what is new?

  2025cites this paper
• FUNDC1: An Emerging Mitochondrial and MAMs Protein for Mitochondrial Quality Control in Heart Diseases

  2023cites this paper
• Study Of (NF- Κb) Gene Expression As A Biomarker For Development Of Cardiovascular Disease In Type 2 Diabetes

  2022cites this paper
• The Role of Mitochondria in Metabolic Syndrome–Associated Cardiomyopathy

  2022cites this paper
• Effects of platelet rich plasma on experimentally induced diabetic heart injury.

  2021cites this paper
• Cathelicidin-WA ameliorates diabetic cardiomyopathy by inhibiting the NLRP3 inflammasome

  2021cites this paper
• The Peroxisome Proliferator-Activated Receptor-Gamma Coactivator-1α–Heme Oxygenase 1 Axis, a Powerful Antioxidative Pathway with Potential to Attenuate Diabetic Cardiomyopathy

  2020cites this paper
• Ameliorative activity of Adansonia digitata fruit on high sugar/high fat diet-simulated Metabolic Syndrome model in male Wistar rats.

  2020cites this paper
• The Potential Cardio-Protective Effects of Canagliflozin alone and in combination with metformin on Fructose induced Insulin resistance in Rats

  2020cites this paper
• Re-evaluating the causes and consequences of non-resolving inflammation in chronic cardiovascular disease

  2019cites this paper
• Qishen Yiqi Drop Pill, a novel compound Chinese traditional medicine protects against high glucose‐induced injury in cardiomyocytes

  2019cites this paper
• Coriolus versicolor alleviates diabetic cardiomyopathy by inhibiting cardiac fibrosis and NLRP3 inflammasome activation

  2019cites this paper
• Reactive Carbonyl Species: Diabetic Complication in the Heart and Lungs.

  2019cites this paper
• Paradigm shift - Metabolic transformation of docosahexaenoic and eicosapentaenoic acids to bioactives exemplify the promise of fatty acid drug discovery.

  2018cites this paper
• TAX1BP1 overexpression attenuates cardiac dysfunction and remodeling in STZ-induced diabetic cardiomyopathy in mice by regulating autophagy.

  2018cites this paper
• Exogenous Pancreatic Kallikrein Improves Diabetic Cardiomyopathy in Streptozotocin-Induced Diabetes

  2018cites this paper
• Diabetic Cardiomyopathy: Impact of Biological Sex on Disease Development and Molecular Signatures

  2018cites this paper
• Inhibition of miR-186-5p contributes to high glucose-induced injury in AC16 cardiomyocytes

  2017cites this paper