Fructose Drives Glucose via Direct Oxidation and Promotes Palmitate/ Oleate Co-Release from Hepg2 Cells: Relevance with the Randle Cycle

Abstract

Background & methods: Evidence indicates that there are significant differences in how glucose and fructose affect host metabolism although the details remain unclear. We determined how liver cells adopt intermediary metabolism to fructose administration. Cultured HepG2 cells were incubated with 5 mM glucose or fructose, above the 5 mM glucose concentration in control cultures. [1,213 C2]-D-glucose was used as the single metabolic tracer. Results: Addition of 5 mM glucose maintained the ratio of complete glucose oxidation to that of other acetateyielding substrates, while addition of 5 mM added fructose significantly decreased 13 CO2 Delta by its contribution to citrate and glutamate in the TCA cycle. Fructose maintained a high rate of direct glucose oxidation via G6PDH which was also seen with glucose-treatment. New palmitate production via fatty acid synthase was significantly increased by both sugars. In contrast to glucose-treatment which resulted in increased intracellular palmitate and oleate content, fructose increased the co-release of newly formed palmitate and oleate into the culture media. Conclusion: These findings demonstrate that fructose rearranges TCA cycle metabolism by providing acetylCoA for oxidation, increasing citrate shuttling and strongly promoting triglyceride efflux of altered de novo synthesis pathways.