Liver and peripheral tissue glycogen metabolism in obese mice: effect of a mixed meal.

Glycogen metabolism in the liver, skeletal muscle, cardiac muscle, and white adipose tissue was studied in gold thioglucose (GTG) obese mice after fasting and during refeeding. Prolonged (48 h) fasted control and GTG mice were refed with standard laboratory diet for 24 h. During fasting and refeeding, the changes in glycogen content and the activity of glycogen synthase I and R and phosphorylase alpha in the liver were similar in lean and GTG mice. However, the glycogen storage in the livers from GTG mice was always greater than that in lean animals. In GTG mice the activity of liver glycogen synthase I and R was significantly higher than that in lean animals 3 and 6 h after refeeding. The activity of liver phosphorylase alpha in GTG mice was higher than that in lean mice after refeeding. There were no significant differences in the glycogen content of white adipose tissue, cardiac muscle, and skeletal muscle from lean and GTG mice during the entire study. The results of this study suggest that increased glycogen storage in the liver is a major alteration in nonoxidative glucose metabolism and contributes to the development of insulin resistance and glucose intolerance in GTG obese mice.