Metabolic toxicity of the heart: insights from molecular imaging.
There is convincing evidence that alterations in myocardial substrate use play an important role in the normal and diseased heart. In this review, insights gained by using quantitative molecular imaging by positron emission tomography and magnetic resonance spectroscopy in the study of human myocardial metabolism will be discussed, and attention will be paid to the effects of nutrition, gender, aging, obesity, diabetes, cardiac hypertrophy, ischemia, and heart failure. The heart is an omnivore organ, relying on metabolic flexibility, which is compromised by the occurrence of defects in coronary flow reserve, insulin-mediated glucose disposal, and metabolic-mechanical coupling. Obesity, diabetes, and ischemic cardiomyopathy appear as states of high uptake and oxidation of fatty acids, that compromise the ability to utilize glucose under stimulated conditions, and lead to misuse of energy and oxygen, disturbing mechanical efficiency. Idiopathic heart failure is a complex disease frequently coexisting with diabetes, insulin resistance and hypertension, in which the end stage of metabolic toxicity manifests as severe mitochondrial disturbance, inability to utilize fatty acids, and ATP depletion. The current literature provides evidence that the primary events in the metabolic cascade outlined may originate in extra-cardiac organs, since fatty acid, glucose levels, and insulin action are mostly controlled by adipose tissue, skeletal muscle and liver, and that a broader vision of organ cross-talk may further our understanding of the primary and the adaptive events involved in metabolic heart toxicity.
Iozzo
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Institute of Clinical Physiology, National Research Council (CNR), Via Moruzzi 1, 56124 Pisa, Italy. patricia.iozzo@ifc.cnr.it
D000255:Adenosine Triphosphate / Q000032:analysis; D000375:Aging / Q000378:metabolism; D003920:Diabetes Mellitus / Q000378:metabolism; D004734:Energy Metabolism; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism; D006331:Heart Diseases / Q000378:metabolism*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism; D010101:Oxygen Consumption; D010725:Phosphocreatine / Q000032:analysis; D049268:Positron-Emission Tomography; D012737:Sex Factors
D005227:Fatty Acids; D010725:Phosphocreatine; D000255:Adenosine Triphosphate; D005947:Glucose