Increase in hepatic gamma-glutamyltransferase (GGT) activity following chronic ethanol intake in combination with a high fat diet.

Increased hepatic gamma-glutamyltransferase (GGT) activity following chronic ethanol consumption has been attributed to enzyme induction, dietary carbohydrate imbalance, and/or to hepatic cell damage. In this study, hepatic GGT activity was increased in rats consuming ethanol (35% of kcals) in a high fat (35% of kcals) diet compared to pair fed and ad lib. fed high fat controls (P less than or equal to 0.01), but no enhancement of activity was observed in those rats consuming ethanol on low fat (11% of kcals) diets. The high-fat-ethanol group also had increased hepatic lipid (P less than or equal to 0.01) and decreased glutathione levels (P less than or equal to 0.05) compared to their ad lib. fed control group. In rats that had ethanol removed from their diet for the final 4 weeks of the 12-week dietary treatment period, levels of GGT, lipid or glutathione were not different from control values. Histochemical evaluation of hepatic GGT activity showed increases associated with centrolobular lipid accumulation in ethanol-fed rats consuming a high fat diet. The cause of the increase in hepatic GGT activity could not be determined from this experiment. However, increased microsomal enzyme activity did not appear to be related to GGT activity. It is suggested that cellular damage following increased lipid accumulation, depletion of hepatic glutathione, or changes in biliary flow may be associated with the increased GGT activity.