Metabolic interactions of parenchymal hepatocytes and dividing epithelial cells in co-culture.

When parenchymal hepatocytes isolated from adult liver are co-cultured with other epithelial cells, the production of various plasma proteins by the hepatocytes is preserved for much longer than in conventional culture. This study examines some of the metabolic interactions between parenchymal hepatocytes and epithelial cells maintained in co-culture. The leakage of lactate dehydrogenase by hepatocytes co-cultured with epithelial cells was lower than in conventional hepatocyte culture. The epithelial cells have a high glycolytic rate and provide the hepatocytes with a continual supply of lactate. The [lactate] was lower in co-cultures of hepatocytes and epithelial cells than in pure epithelial cultures of similar density, suggesting lactate clearance by the hepatocytes. Alanine uptake was higher in conventional hepatocyte cultures, which lack an exogenous supply of lactate, than in parenchymal hepatocytes in co-culture. Studies with pure parenchymal hepatocytes incubated with increasing [lactate] suggest that lactate is utilized in preference to alanine as a gluconeogenic substrate by hepatocytes co-cultured with epithelial cells. Ketogenesis and carnitine palmitoyltransferase activity declined more slowly in hepatocytes co-cultured with epithelial cells than in conventional culture. It is concluded that the co-culture model has potential for long-term studies of carbohydrate and lipid metabolism.