Opposing Effects of Chronic Alcohol Consumption on Hepatic Gluconeogenesis for Female Versus Male Rats

Abstract: Background: The impact of chronic alcohol consumption on hepatic gluconeogenesis (HGN) between males and females is unknown. To determine the effects of chronic alcohol consumption (8 weeks) on HGN, the isolated liver perfusion technique was used on 24-hr-fasted male and female Wistar rats. Methods: After surgical isolation, livers were perfused (single pass) for 30 min with Krebs-Henseleit bicarbonate buffer and fresh bovine erythrocytes with no added substrate (washout period). After the washout period, livers were perfused with lactate (10 mM) and [U-14C]lactate (15,000 dpm/ml) using the recirculation method. Results: There was no significant difference in HGN between males and females fed the control diet. In contrast, the females chronically fed the ethanol diet (FE) had significantly lower HGN rates (2.73 ± 0.37 μmol/min × g liver protein−1), whereas males fed the ethanol diet (ME) had significantly higher HGN rates (4.99 ± 0.45 μmol/min × g liver protein−1) than controls (3.83 ± 0.34 μmol/min × g liver protein−1). Concomitant decreases were also observed for both 14C-lactate incorporation into 14C-glucose and rates of lactate uptake for FE, while corresponding increases were observed for 14C-lactate incorporation into 14C-glucose for ME. The livers from ME were able to convert a greater percentage of the lactate into glucose, resulting in the elevation in gluconeogenic capacity. Conclusion: Chronic alcohol consumption lowers the hepatic gluconeogenic capacity from lactate in females and elevates HGN in males.