Chronic ethanol consumption and liver glycogen synthesis

Chronic ethanol consumption results in a dramatic decrease in liver glycoge n concentrations, which could be related to either a depressed rate of synt hesis or an increased rate of breakdown. Earlier studies suggested that the re is not an increase in the rate of glycogenolysis as glycogen phosphoryla se activities are not elevated. In the present study it was observed that t he incorporation of radiolabeled glucose into glycogen was significantly de pressed in hepatocytes from ethanol-fed rats under both anaerobic and aerob ic conditions. Chronic ethanol consumption decreased the total glycogen syn thase (a + b) activity, which correlated closely with a loss in glycogen sy nthase protein. However, glycogen synthase messenger RNA levels were not de pressed, which indicated posttranscriptional modifications affecting both a ctivity and protein levels. The concentration of glucose transporter 1 was also decreased due to ethanol consumption, but glucose transporter 2 levels were not altered. This latter result suggests that glucose transport in th e perivenous region of the liver lobule may be decreased in chronic ethanol consumers. The alterations in glucose transport protein and glycogen synth esis observed in this study may contribute to lowered glycogen synthesis, b ut do not appear to account for the magnitude of the decreases in glycogen levels and rate of synthesis. Indeed, ethanol effects on glycogen metabolis m are likely to be exerted at several levels, including posttranslational m odulation of enzyme activities. (C) 2001 Academic Press.