Abstract
Carbohydrates and long-chain fatty acids are the predominant substrates for cardiac energy production. While the mechanism and regulation of myocardial carbohydrate (glucose, lactate) uptake have been unraveled in detail in the 1990s, insight into fatty acid uptake originates from more recent studies. Fatty acid movement across the sarcolemma is facilitated by membrane-associated proteins, specifically CD36, membrane-associated fatty acid-binding protein (FABPpm) and selected fatty acid transport protein (FATP) isoforms, and is up- or downregulated through changes in sarcolemmal content of (primarily) CD36. The recruitment of CD36 from an endosomal storage pool to the sarcolemma, which is under the control of various physiological stimuli (including insulin and contraction), represents a pivotal step in the overall regulation of myocardial fatty acid uptake and utilization. Dysregulation of the intracellular cycling of CD36 underlies various cardiac metabolic diseases. As a result, the mechanism and regulation of myocardial glucose uptake by GLUT4 cycling and of fatty acid uptake by CD36 cycling are very similar. Likely, manipulation of the presence and/or activity of substrate transporters for glucose and fatty acids in the sarcolemma holds promise as therapeutic approach to alter cardiac substrate preference in disease so as to regain metabolic homeostasis and rectify cardiac functioning.
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Glatz, J.F.C., Luiken, J.J.F.P. (2014). Control of Myocardial Fatty Acid Uptake. In: Lopaschuk, G., Dhalla, N. (eds) Cardiac Energy Metabolism in Health and Disease. Advances in Biochemistry in Health and Disease, vol 11. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-1227-8_4
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