Glutamine and fatty acid oxidation are the main sources of energy for Kupffer and endothelial cells

This study assessed and compared the rate of glucose utilization, activity of the hexose-monophosphate shunt (HMS), and the oxidation of glutamine, lactate, and palmitate in Kupffer (KC), endothelial (EC), and parenchymal liver cells (PC). Cells were isolated by collagenase and pronase digestion followed by centrifugal elutriation. The freshly isolated cells were incubated in the presence of 5 mM glucose, 0.5 mM glutamine, 1 mM lactate, and 0.4 mM palmitate, and the oxidation rate of individual substrates was determined by the measurement of ¹⁴CO₂ production. Glucose utilization was assessed by detritiation of [2-³H]glucose. Glucose flux through HMS was 2.6, 1.6, and 0.72 nmol·h^-1·mg protein^-1 in KC, EC, and PC, respectively. The oxidation rate of palmitate in PC (3.5 nmol·h^-1·mg protein^-1) was about twofold greater than in nonparenchymal cells. Glutamine oxidation was 6.1, 4.2, and 2.1 nmol·h^-1·mg protein^-1 in KC, EC, and PC, respectively. In contrast, oxidation of exogenous lactate by PC (32.1 nmol·h^-1·mg protein^-1) was about seven- to eightfold greater than by KC or EC. Presence of prevailing lactate concentrations did not inhibit glucose oxidation in these cells, while it attenuated glucose utilization by PC. Our data show that in the presence of a physiological substrate mixture, <20% of the ATP generated from exogenous substrates is derived from glycolysis in KC or EC. Oxidation of glutamine and palmitate are the main sources for energy in these cells. In PC, however, lactate and palmitate oxidation is responsible for ~90% of the ATP production derived from the oxidation of exogenous substrates. Our data also indicate that glutamine is an important source for the citric acid cycle intermediates in the nonparechymal cells of the liver.