Sources of Hepatic Glycogen Synthesis in Mice Fed with Glucose or Fructose As the Sole Dietary Carbohydrate

Purpose: The positional analysis of hepatic glycogen enrichment from deuterated water ( H O) by H NMR has been applied previously to resolve the contributions of glucose and fructose to glycogen synthesis in rodents fed a high sucrose diet. To further validate this method, this analysis was applied to mice fed with synthetic diets whose carbohydrate components consisted solely of either glucose or fructose.

Methods: Eight glucose-fed and 12 fructose-fed mice were given H O followed by ad libitum feeding overnight. Mice were then euthanized, hepatic glycogen was isolated and derivatized to monoacetone glucose, and H-enrichment of positions 2, 5, and 6 were measured by H NMR. From these data, the fraction of overnight glycogen appearance from the direct pathway and/or glycogen cycling and indirect pathway were estimated. Indirect pathway fractions were resolved into Krebs cycle and triose-phosphate sources-the latter including contributions from fructose metabolism.

Results: After overnight feeding, the fraction of overnight glycogen appearance derived from direct pathway and/or glycogen cycling in glucose-fed-mice was 63 ± 1%. For the indirect pathway, Krebs cycle and triose-phosphate sources contributed 22 ± 1% and 15 ± 1%, respectively. For fructose-fed-mice, glycogen appearance was dominated by triose-phosphate sources (60 ± 2%) with lesser contributions from Krebs cycle (14 ± 1%) and direct and/or glycogen cycling (26 ± 2%).

Conclusions: H NMR analysis of hepatic glycogen H enrichment from H O provides realistic profiles of dietary glucose and fructose contributions to hepatic glycogen synthesis in mice fed with diets containing 1 or the other sugar as the sole carbohydrate source.