Lipotoxicity in obesity and diabetes-related cardiac dysfunction |
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| Institution: | 1. Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB, Canada;2. Alberta Diabetes Institute, University of Alberta, Edmonton, AB, Canada;1. Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, Den Dolech 2, 5612 AZ Eindhoven, The Netherlands;2. Department of Pediatrics, Center for Liver, Digestive and Metabolic Diseases, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands;3. Department of Molecular Genetics, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands;1. Ph.D. Program for Aging, China Medical University, Taichung, Taiwan;2. Division of Cardiology, Department of Internal Medicine, China Medical University Hospital, China Medical University, Taichung, Taiwan;3. Department of Nursing, Mei Ho University, Pingguang Road, Pingtung, Taiwan;4. Department of pathology, Changhua Christian Hospital, Changhua, Taiwan;5. Jen-Teh Junior College of Medicine, Nursing and Management, Miaoli, Taiwan;6. Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan;7. Chinese Medicine Department, China Medical University Beigang Hospital, Taichung, Taiwan;8. Department of Biotechnology, Bharathiar University, Coimbatore -641 046, India;9. Department of Biological Science and Technology, China Medical University, Taichung, Taiwan;10. Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan;11. Graduate Institute of Chinese Medical Science, China Medical University, Taichung, Taiwan;12. Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan |
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| Abstract: | Patients with type 2 diabetes (T2D) are at increased risk for cardiovascular diseases including diabetic cardiomyopathy, which is ventricular dysfunction independent of underlying coronary artery disease and/or hypertension. With numerous advancements in our ability to detect ventricular dysfunction, as well as the molecular mechanisms contributing to ventricular dysfunction in diabetic patients, it is now appreciated that diabetic cardiomyopathy is becoming more prevalent in our population. In spite of these advancements, we do not have any specific therapies currently approved for treating this condition. As obesity increases the risk for both T2D and cardiovascular disease, it has been postulated that obesity-mediated alterations in myocardial lipid metabolism are critical to the pathophysiology of diabetic cardiomyopathy. Indeed, animal studies have provided strong evidence that alterations in either myocardial fatty acid uptake or fatty acid β-oxidation lead to the accumulation of various lipid intermediates including triacylglycerol, diacylglycerol, ceramide, long-chain acyl CoA, acylcarnitine, and many others that are tightly linked to the progression of ventricular dysfunction. We review herein why lipid intermediates accumulate in the heart during obesity and/or T2D, with a focus on which of these various lipid intermediates may be responsible for cardiac lipotoxicity, and whether findings in animal models are relevant to humans. An improved understanding of how these lipid intermediates accumulate in the heart and how they produce cardiac toxicity may lead to the discovery of novel targets to pursue for the treatment of human diabetic cardiomyopathy. This article is part of a Special Issue entitled: Heart Lipid Metabolism edited by G.D. Lopaschuk. |
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