Regulation of hepatic secretion of apolipoprotein B-containing lipoproteins: information obtained from cultured liver cells.
A major theme of this review is that apoB secretion is regulated post-translationally, and that apoB secretion reacts rapidly to the current state of lipid metabolism in the cell. Therefore, as discussed by Fungwe et al. (122), the metabolism of triglyceride and of cholesteryl ester, in so far as both can be used as core lipids for apoB-containing LPs, are inextricably linked, and the shortage of one or both of these lipids could, by "allowing" increased intracellular degradation in the ER, inhibit the secretion of apoB. Another theme in this review is that the regulation of apoB secretion may be quite different in rat hepatocytes compared to cultured cells (HepG2) used as a model for human hepatocytes. Exogenous fatty acids appear to modulate the rate of apoB secretion in HepG2 cells, whereas they have only minimal effects on apoB secretion in rat hepatocytes or liver. Increased dietary cholesterol, on the other hand, appears to be an important modulator of apoB secretion in rats, but the evidence for effects of cholesterol on apoB secretion in HepG2 cells is less convincing. Finally, because HepG2 cells are an immortalized cell line, there could be many differences between these cells and human hepatocytes in vivo. Therefore, many of the results obtained with HepG2 cells should be corroborated in primary cultures of human hepatocytes. However, investigators utilizing primary human hepatocytes should be sure that the culture conditions are adequate to maintain the continued transcription of liver specific genes and to prevent the dedifferentiation of these cells in culture (85, 86).
Department of Food Science and Human Nutrition, University of Missouri, Columbia 65211.
J L
JL
Dixon
H N
HN
Ginsberg
D001055:Apolipoproteins B / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular; D002478:Cells, Cultured; D006706:Homeostasis; D006801:Humans; D050356:Lipid Metabolism; D008074:Lipoproteins / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008113:Liver Neoplasms; D011499:Protein Processing, Post-Translational; D014407:Tumor Cells, Cultured
D001055:Apolipoproteins B; D008074:Lipoproteins