The glucose storage polymer glycogen is generally considered to be an important source of energy for skeletal muscle contraction and a factor in exercise endurance. A genetically modified mouse model lacking muscle glycogen was used to examine whether the absence of the polysaccharide affects the ability of mice to run on a treadmill. The MGSKO mouse has the GYS1 gene, encoding the muscle isoform of glycogen synthase, disrupted so that skeletal muscle totally lacks glycogen. The morphology of the soleus and quadriceps muscles from MGSKO mice appeared normal. MGSKO-null mice, along with wild type littermates, were exercised to exhaustion. There were no significant differences in the work performed by MGSKO mice as compared with their wild type littermates. The amount of liver glycogen consumed during exercise was similar for MGSKO and wild type animals. Fasting reduced exercise endurance, and after overnight fasting, there was a trend to reduced exercise endurance for the MGSKO mice. These studies provide genetic evidence that in mice muscle glycogen is not essential for strenuous exercise and has relatively little effect on endurance.The two major repositories of glycogen, the polymeric storage form of glucose, are in the liver and skeletal muscle (1). In humans, these carbohydrate reserves are an important determinant of endurance upon sustained exercise, and muscle glycogen has long been viewed as a critical energy source during muscular activity (2-4). Depletion of muscle glycogen results in fatigue and impaired muscle performance and is a major determinant of endurance (2-5). Likewise, the ineffective utilization of muscle glycogen, as in patients with McArdle disease, leads to impaired exercise tolerance (6). In their "glycogen shunt" hypothesis, Shulman and Rothman (7) propose that glycogenolysis is the predominant source of energy for muscle contraction with glycogen acting essentially as an intermediate for blood glucose to enter glycolysis. Increasing muscle glycogen by manipulating diet and exercise regimens, a procedure termed "carbohydrate loading" or "glycogen supercompensation" (8), is adopted by endurance athletes to delay the onset of fatigue (4, 9 -11).Although the importance of adequate muscle glycogen to sustain exercise in humans has been well documented, caution is needed in extrapolating findings in rodents to humans. For instance, the amount of muscle glycogen, expressed as a fraction of body mass, is ϳ10-fold lower in mice than in humans (12, 13), whereas the corresponding values for liver glycogen are comparable (14). Thus, the relative role of these two glycogen storage depots may be different between the two species. The relative importance of muscle and liver glycogen stores as fuel sources for exercise has been studied extensively in rats (15-17). Exhaustive exercise either by treadmill running or swimming resulted in a reduction of muscle glycogen by 70 or Ͼ90%, respectively (15, 16). Both exercise methods reduced liver glycogen Ͼ90%. Using less strenuous exercise regimens, muscle g...

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