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 ( 2 H 2 O) by 2 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 2 H 2 O followed by ad libitum feeding overnight. Mice were then euthanized, hepatic glycogen was isolated and derivatized to monoacetone glucose, and 2 H‐enrichment of positions 2, 5, and 6 S were measured by 2 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 2 H NMR analysis of hepatic glycogen 2 H enrichment from 2 H 2 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.