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

We used dynamic in vivo P-31 magnetic resonance spectroscopy to noninvasive ly study the metabolism of glycerol by the liver in living rats, as a means of detecting subtle metabolic changes induced by chronic ethanol consumpti on. Rats subjected to chronic ethanol consumption and their pair-fed contro ls were given a metabolic load of glycerol (0.75 or 1.3 mL glycerol.kg body mass(-1), i.p. or i.v) under normoxic or hyperoxic (98% O-2) conditions. C hanges in the level of glycerol 3-phosphate were followed in situ by monito ring the hepatic P-31 phosphomonoester resonance every 7 or 13 min for up t o 330 min. When challenged with a large dose of glycerol, chronic ethanol-t reated rats exhibited less accumulation of glycerol 3-phosphate than contro ls, independent of the route of administration of the glycerol or whether t he two groups were fasted or fed. For example, 1.3 mL glycerol.kg(-1) i.v. under normoxic conditions resulted in a two-fold increase in phosphomonoest er in ethanol-treated rats compared with a five-fold increase in controls. The ethanol-treated rats also showed a slower rate of phosphorylation of gl ycerol and slower oxidation of glycerol 3-phosphate than controls, indicati ng decreased activities of the glycerol kinase and glycerol 3-phosphate deh ydrogenase steps, and hence slower glycerol utilization. The rate of glycer ol utilization was dose and oxygen concentration dependent. Kinetic analysi s indicated that the chronic ethanol-induced decrease in the glycerol 3-pho sphate dehydrogenase reaction was due to a decreased rate of NADH reoxidati on in the liver, likely owing to a decrease in oxygen supply or utilization in the ethanol-treated rats. These observations support the hypothesis of preexisting hypoxia in rat liver after chronic ethanol administration. This study demonstrates the utility of dynamic in vivo P-31 magnetic resonance spectroscopy in following the metabolism of a glycerol load as a sensitive, nonperturbing, and potentially clinically applicable test of liver functio n.