Mechanism of triglyceride accumulation in rat preadipocyte cultures exposed to very low density lipoprotein.

Cultured preadipocytes derived from the stromal-vascular fraction of adipose tissue have been shown to accumulate sufficient triglycerides to assume adipocyte morphology when exposed to high concentrations of very low density lipoprotein. Since these cells synthesize and secrete lipoprotein lipase it was of interest to determine whether the accumulation of intracellular triglyceride originated from the uptake of products of the lipase reaction or whether the cells were utilizing intact lipoprotein particles. Upon incubation of preadipocytes with very low density lipoprotein, the triglyceride disappeared from the medium and accumulated in the cells. This response was accentuated by the addition of heparin to the culture medium. Balance studies conducted in the presence of heparin demonstrated that the loss of medium triglyceride could account for the increase in cell stores. Quantitative studies demonstrated that the increase in cellular triglyceride was a result of the cellular uptake and reesterification of the fatty acids liberated from very low density lipoprotein triglycerides by the action of cellular lipoprotein lipase. The magnitude of the cellular response was dependent on the concentration of fetal bovine serum in the incubation medium and increased as the serum level decreased. Likewise, when albumin was substituted for the serum, increasing amounts of albumin decreased the cellular triglyceride accumulation. It was concluded that the presence of albumin in the culture medium modulated cellular triglyceride accumulation by 1) influencing the extent of triglyceride lipolysis and 2) by regulating the uptake of liberated fatty acid into the cells. Experiments using very low density lipoprotein containing radiolabeled triglyceride and cholesteryl esters demonstrated that the uptake of the very low density lipoprotein or the remnant particle produced by the action of lipase did not significantly contribute to the accumulation of triglyceride in the cells.