Time-dependent effect of ethanol force-feeding on glycogen repletion: NMR evidence of a link with ATP turnover in rat liver

Abstract The purpose was to study the hepatic effects of low-dose ethanol on the links between ATP and glycogen production. Fasted male Wistar rats received a single force-feeding of glucose plus ethanol or isocaloric glucose. At different times after force-feeding (0–10 h), glycogen repletion and ATP characteristics (content, apparent catalytic time constant, mitochondrial turnover) were monitored by 13 C- or 31 P-nuclear magnetic resonance (NMR) in perfused and isolated liver. In vivo glycogen repletion after force-feeding was slower after glucose plus ethanol vs. glucose (12.04 ± 0.68 and 8.50 ± 0.86 μmol/h/g liver wet weight [ww], respectively), reaching a maximum at the 6th hour. From the 3rd to the 8th hour, glycogen content was lower after glucose plus ethanol vs. glucose. After glucose plus ethanol, the correlation between glycogen and ATP contents presented two linear steps: before and after the 3rd hour (30 and 102 μmol glycogen/g ww per μmol ATP/g ww, respectively, the latter being near the single step measured in glucose). After glucose plus ethanol, ATP turnover remained stable for 2 h, was 3-fold higher from the 3rd hour to the 8th hour, and was higher than after glucose (2.59 ± 0.45 and 1.39 ± 0.19 μmol/min/g ww, respectively). In the 1st hour, glucose plus ethanol induced a transient acidosis and an increase in the phosphomonoesters signal. In conclusion, after ethanol consumption, a large part of the ATP production was diverted to redox re-equilibrium during the first 2 h, thereby reducing the glycogen synthesis. Thereafter, the maintenance of a large oxidative phosphorylation allowed the stimulation of glycogen synthesis requiring ATP.