Chronic ethanol administration alters hepatic rates of glycerol phosphorylation and glycerol 3-phosphate oxidation: a dynamic in vivo 31P magnetic resonance spectroscopy study.

We used dynamic in vivo 31P magnetic resonance spectroscopy to noninvasively study the metabolism of glycerol by the liver in living rats, as a means of detecting subtle metabolic changes induced by chronic ethanol consumption. Rats subjected to chronic ethanol consumption and their pair-fed controls were given a metabolic load of glycerol (0.75 or 1.3 mL glycerol x kg body mass(-1), i.p. or i.v) under normoxic or hyperoxic (98% O2) conditions. Changes in the level of glycerol 3-phosphate were followed in situ by monitoring the hepatic 31P phosphomonoester resonance every 7 or 13 min for up to 330 min. When challenged with a large dose of glycerol, chronic ethanol-treated rats exhibited less accumulation of glycerol 3-phosphate than controls, independent of the route of administration of the glycerol or whether the two groups were fasted or fed. For example, 1.3 mL glycerol x kg(-1) i.v. under normoxic conditions resulted in a two-fold increase in phosphomonoester in ethanol-treated rats compared with a five-fold increase in controls. The ethanol-treated rats also showed a slower rate of phosphorylation of glycerol and slower oxidation of glycerol 3-phosphate than controls, indicating decreased activities of the glycerol kinase and glycerol 3-phosphate dehydrogenase steps, and hence slower glycerol utilization. The rate of glycerol utilization was dose and oxygen concentration dependent. Kinetic analysis indicated that the chronic ethanol-induced decrease in the glycerol 3-phosphate dehydrogenase reaction was due to a decreased rate of NADH reoxidation in the liver, likely owing to a decrease in oxygen supply or utilization in the ethanol-treated rats. These observations support the hypothesis of pre-existing hypoxia in rat liver after chronic ethanol administration. This study demonstrates the utility of dynamic in vivo 31P magnetic resonance spectroscopy in following the metabolism of a glycerol load as a sensitive, nonperturbing, and potentially clinically applicable test of liver function.