Objectives: 

Enrichment of hepatic glycogen from deuterated water (2H2O) during feeding informs the sources of its synthesis. Hepatic glycogen can be derived from glucose via the direct pathway and from 3-carbon precursors via the indirect pathway. Indirect pathway sources can include gluconeogenic substrates derived via the Krebs cycle as well as substrates that enter as triose-P, such as glycerol and fructose. For animals whose food was supplemented with sucrose, we show that the contribution of fructose to hepatic glycogen synthesis can be resolved from that of glucose and other precursors.

Materials: 

Six Wistar rats were placed on normal chow (NC) and seven on normal chow with their drinking water supplemented with 35% sucrose (HS) for 14 days. 2H2O was injected on day 13, then on day 14, liver glycogen was analyzed post-mortem for 2H-enrichment. Contributions of direct and indirect pathways were quantified from the ratio of positions 5 and position 2 enrichments. Contributions of Krebs cycle and Triose-P sources to glycogen were estimated from the difference between positions 5 and 6 enrichments of glycogen. Glycogen synthesis contributions reported as micromol/g dry wt. liver.

Results: 

Estimation of direct pathway, Krebs cycle and Triose-P contributions yield significantly different profiles of glycogen synthesis for NC and HS animals. Overnight glycogen synthesis tended to be higher for HS versus NC (259 ± 34 vs. 156 ± 36, p = 0.06). Direct pathway and Krebs cycle contributions were equal for both diets (96 ± 34 and 36 ± 7, respectively, for HS; 81 ± 17 and 43 ± 14 respectively,for NC). However, HS had a significantly higher contribution from Triose-P sources compared to NC (127 ± 22 vs. 32 ± 10, p < 0.01).

Conclusions: 

Enrichment of hepatic glycogen from 2H2O informs its sources of synthesis in naturally-feeding rats. When standard chow was supplemented with sucrose, there was a significant increase in the indirect pathway flux that was dominated by contributions from the fructose moiety of sucrose.