Divergent responses of the liver to increased delivery of glucose or fatty acids: implications for the pathogenesis of type IV hyperlipoproteinemia

Abstract

This study examines the patterns of response of primary cultures of hamster hepatocytes to increased delivery of glucose or oleate. Increased glucose in the medium produced: (1) increased triglyceride in the cells and the medium; (2) no change in cholesterol ester in the cells or the medium; (3) no change in apo B100 secreted into the medium; (4) more apo B100 particles within the VLDL range with an increase in the VLDL triglyceride to apo B100 ratio. By contrast, increased oleate in the medium resulted in: (1) increased triglyceride in the cells and the medium; (2) increased cholesterol ester in the cells and the medium; and (3) increased apo B100 secreted into the medium. Important differences in the intracellular metabolism of triglyceride and cholesterol ester were also documented. Under all circumstances, there was substantially more radiolabelled triglyceride (overall eight times more) in the cell than in the medium, indicating that up to 90% of the newly synthesized triglyceride enters the cellular pool rather than being secreted with apo B100. By contrast, almost half of the newly synthesized cholesterol ester molecules were secreted with apo B100, pointing to an equal probability of entering the cell storage pool as opposed to being secreted. The data establish therefore two patterns of response of the liver to increased triglyceride synthesis depending on whether the substrate drive is glucose or oleate.