Reduced Muscle Glycogen Differentially Affects Exercise Performance and Muscle Fatigue

This investigation examined the effects of reduced muscle glycogen on exercise performance and muscle fatigue. Male rats were assigned to a low glycogen group (LG) that participated in a protocol of exercise and fasting, a high glycogen group (HG) that exercised but were allowed free access to food, or control group (CON) that did not exercise but were allowed free access to food. Following the protocol, muscle glycogen content of the LG animals was reduced by 45%. The LG animals also performed 79 and 81% less voluntary treadmill exercise than the HG and CON groups. At exhaustion, the LG group had lower blood glucose than HG and CON but exhibited no reduction in sarcoplasmic reticulum (SR) function. During 30？min of in situ stimulation, the rates and magnitudes of muscle fatigue were not significantly different between groups, and fatigue-induced reductions in SR function were similar between groups. The results indicate that reduced muscle glycogen markedly impairs voluntary exercise performance but does not appreciably affect isolated muscle function. It is likely that exercise exhaustion due to reduced muscle glycogen is due, in large part, to hypoglycemia and central fatigue as opposed to peripheral mechanisms. 1. Introduction As early as the 19th century a relationship between carbohydrate metabolism and fatigue was proposed. In 1807, Berzelius suggested “the amount of free lactic acid in skeletal muscle is proportional to the extent to which it has been exercised” [1]. Exhaustive exercise is known to cause to dramatic reductions in muscle glycogen content within the active muscle [2–4]. Also, the onset of exhaustion is dependent on the initial muscle glycogen content [2] and dietary manipulation of muscle glycogen can increase or decrease exercise duration [5]. Based on this, most researchers readily accept the notion that muscle glycogen depletion is somehow involved in the development of fatigue during prolonged exercise. Despite this, more than 40 years of investigation have failed to identify a specific “cause-and-effect” relationship between muscle glycogen and fatigue during exercise. Newsholm and Leech [6] proposed that during muscular activity, the loss of glycogen results in an inability to sustain an adequate glycolytic flux rate to support ATP regeneration. Reductions in ATP resynthesis would then cause a decline in intracellular ATP concentration, resulting in an inability to meet the energy demands of the contraction process. As a consequence, the muscle would be unable to sustain maximal force output. Green [7] defined this notion as