Changes in glycogen metabolism in liver of gold thioglucose injected mice during the development of obesity.

A study of glycogen metabolism in the liver has been carried out in gold thioglucose (GTG) injected mice during the development of obesity. In GTG obese mice, overt obesity, hyperglycaemia and hyperinsulinaemia had developed by 6 weeks after the injection of GTG. Beyond 6 weeks after GTG injection, the gain of body weight and increment in serum glucose and insulin levels with age in obese mice were not obvious when compared with those of age-matched control animals. The glycogen concentration, total glycogen storage, activity of glycogen synthase R and activity of phosphorylase a in the liver from GTG obese mice were significantly greater than those in lean mice from 2-4 weeks after GTG injection and remained higher thereafter. These results demonstrate that the increased liver glycogen storage and increased activity of glycogen synthase and phosphorylase occur early in the development of obesity and at a similar time to previously reported increases in pyruvate dehydrogenase activity (Caterson et al. (1987) Biochem. J. 243, 549-553) and lipid synthesis in liver (Cooney et al. (1989) Biochem. J. 259, 651-657). The emergence of these abnormalities in glycogen metabolism early in the development of obesity may contribute to the establishment of glucose intolerance and insulin resistance in this model of obesity which became apparent at approximately the same time after GTG injection.