INHIBITION OF GLYCEROL METABOLISM IN HEPATOCYTES ISOLATED FROM ENDOTOXIC RATS

Sepsis or endotoxaemia inhibits gluconeogenesis from various substrate s, the main effect being related to a change in the phosphoenolpyruvat e carboxykinase transcription rate. In addition, sepsis has been repor ted to affect the oxidative phosphorylation pathway. We have studied g lycerol metabolism in hepatocytes isolated from rats fasted and inject ed 16 h previously with lipopolysaccharide from Escherichia coli. Endo toxin inhibited glycerol metabolism and led to a very large accumulati on of; glycerol 3-phosphate; the cytosolic reducing state was increase d. Furthermore glycerol kinase activity was increased by 33% (P<0.01). The respiratory rate of intact cells was significantly decreased by s epsis, with glycerol or octanoate as exogenous substrates, whereas oxi dative phosphorylation (ATP-to-O ratio or respirations in state 4, sta te 3 and the oligomycin-insensitive state as well as the uncoupled sta te) was unchanged in permeabilized hepatocytes. Hence the effect on en ergy metabolism seems to be present only in intact hepatocytes. An add itional important feature was the observation of a significant increas e in cellular volume in cells from endotoxic animals, which might acco unt for the alterations induced by sepsis.