2H enrichment distribution of hepatic glycogen from 2H2O reveals the contribution of dietary fructose to glycogen synthesis

Delgado TC, Martins FO, Carvalho F, Goncalves A, Scott DK, O'Doherty R, Macedo MP, Jones JG. H-2 enrichment distribution of hepatic glycogen from (H2O)-H-2 reveals the contribution of dietary fructose to glycogen synthesis. Am J Physiol Endocrinol Metab 304: E384-E391, 2013. First published December 4, 2012; doi:10.1152/ajpendo.00185.2012.-Dietary fructose can benefit or hinder glycemic control, depending on the quantity consumed, and these contrasting effects are reflected by alterations in postprandial hepatic glycogen synthesis. Recently, we showed that H-2 enrichment of glycogen positions 5 and 2 from deuterated water ((H2O)-H-2) informs direct and indirect pathway contributions to glycogenesis in naturally feeding rats. Inclusion of position 6(S) H-2 enrichment data allows indirect pathway sources to be further resolved into triose phosphate and Krebs cycle precursors. This analysis was applied to six rats that had fed on standard chow (SC) and six rats that had fed on SC plus 35% sucrose in their drinking water (HS). After 2 wk, hepatic glycogenesis sources during overnight feeding were determined by (H2O)-H-2 administration and postmortem analysis of glycogen H-2 enrichment at the conclusion of the dark period. Net overnight hepatic glycogenesis was similar between SC and HS rodents. Whereas direct pathway contributions were similar (403 +/- 71 mu mol/g dry wt HS vs. 578 +/- 76 mu mol/g dry wt SC), triose phosphate contributions were significantly higher for HS compared with SC (382 +/- 61 vs. 87 +/- 24 mu mol/g dry wt, P < 0.01) and Krebs cycle inputs lower for HS compared with SC (110 +/- 9 vs. 197 +/- 32 mu mol/g dry wt, P < 0.05). Analysis of plasma glucose H-2 enrichments at the end of the feeding period also revealed a significantly higher fractional contribution of triose phosphate to plasma glucose levels in HS vs. SC. Hence, the H-2 enrichment distributions of hepatic glycogen and glucose from (H2O)-H-2 inform the contribution of dietary fructose to hepatic glycogen and glucose synthesis.