In contrast to the liver and kidneys, the heart is not a gluconeogenic organ. And strictly speaking in terms of the mobilization of endogenous energy sources, it is apparent that mobilization of intramuscular triglyceride can result in mobilization of fatty acids within the heart even though it is a net consumer of fatty acids from the systemic circulation ( 11).Ī unique reason to emphasize cardiac lactate metabolism in this paper is that of the purported functions of lactate shuttling (energy substrate, gluconeogenic precursor, signaling molecule), studies indicate that the heart depends heavily on exogenous lactate as a fuel when cardiac work is elevated. ![]() Hence, glycogen is not known to be a major energy source for the healthy heart. The cardiac glycogen pool probably turns over, just as in skeletal muscle ( 13), but degradation in excess of synthesis is not as exaggerated as in working skeletal muscle ( 14). As previously shown for skeletal muscle and whole-body metabolism ( 8), changes in cardiac work determine the rates and relative uses of energy substrates, with lesser work emphasizing lipid oxidation ( 9– 12) and greater work emphasizing carbohydrate (i.e., glucose and lactate) energy sources ( 10, 12). ![]() The heart is also regarded as a “pay as you go” energy consumer because it relies heavily on exogenous as opposed to endogenous energy sources. In terms of fuel energy substrate use, the heart is sometimes referred to as “omnivorous,” meaning it can simultaneously oxidize a variety of energy substrates including glucose, lactate, fatty acids, and ketones. Beyond the important role of lactate in supporting cardiac functioning, examination of the role of lactate in cardiac metabolism is illustrative overall regulation of energy substrate partitioning in other body tissues and organs. While extensive data have been presented to support the lactate shuttle hypothesis in humans in vivo, little had been written to describe the role of lactate in cardiac metabolism or the role of the heart in terms of overall, whole body–energy substrate balance. No longer thought of as a dead-end metabolite, a fatigue agent, and metabolic poison, in contemporary physiology, lactate is seen as a major metabolic intermediate that has wide-ranging impacts in energy substrate distribution and utilization, gluconeogenesis, and cell signaling ( 1, 2, 5, 6). The purported role of lactate in physiology and medicine is a century old, but understanding of the role has changed dramatically in the last three decades ( 1– 7). Specifically, interruption of blood flow during the isotonic phase of systole is supported by glycolysis and subsequent return of blood flow during diastole allows for recovery sustained by oxidative metabolism. Therefore, the presence of an intra-cardiac lactate shuttle is posited to explain how cardiac mechanics and metabolism are synchronized. Now, with greater scrutiny and recognition of the effect of the cardiac cycle on myocardial blood flow, there brings an appreciation that metabolic fluxes must accommodate to pressure-flow realities within an organ in which they occur. ![]() The exchange of mass represented a conservation of mass that required the integration of neuroendocrine, autoregulatory, and cardiovascular systems. One powerful example of cell–cell lactate shuttling was the exchange of carbohydrate energy in the form of lactate between working limb skeletal muscle and the heart. ![]() Recognition of lactate shuttling came first in studies of physical exercise where the roles of driver (producer) and recipient (consumer) cells and tissues were obvious. Cell–cell and intracellular lactate shuttles in the heart and between the heart and other tissues fulfill essential purposes of energy substrate production and distribution as well as cell signaling under fully aerobic conditions. Exercise Physiology Laboratory, Department of Integrative Biology, University of California, Berkeley, Berkeley, CA, United StatesĪfter almost a century of misunderstanding, it is time to appreciate that lactate shuttling is an important feature of energy flux and metabolic regulation that involves a complex series of metabolic, neuroendocrine, cardiovascular, and cardiac events in vivo.
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