Abstract
Despite a complete lack of microsomal triglyceride transfer protein (MTP), L35 rat hepatoma cells secrete triglyceride-containing lipoproteins, albeit at a rate 25% of that of parental FAO hepatoma cells, which express high levels of MTP. The inability to express MTP was associated with a complete block in the secretion of both apolipoprotein (apo)B-100 and apoB-48. Stable expression of a MTP transgene restored the secretion of both apoB-100 and apoB-48 in L35 cells, indicating that MTP is essential for the secretion of both forms of apoB. Treatment with the MTP inhibitor BMS-200150 reduced the secretion of triglyceride by 70% in FAO cells, whereas the inhibitor did not affect the secretion of triglycerides by L35 cells. Thus, in the presence of the MTP inhibitor, both cell types secreted triglycerides at similar rates. Essentially, all of the triglycerides secreted by L35 cells were associated with HDL containing apoA-IV and apoE but devoid of apoB-100 or apoB-48. These results suggest that these triglyceride-containing lipoproteins are assembled and secreted via a pathway that is independent of both apoB and MTP. Our findings support the concept that apoB and MTP co-evolved and provided a means to augment the secretion of triglyceride through the formation of lipoproteins containing large hydrophobic cores enriched with triglycerides.—Hui, T. Y., L. M. Olivier, S. Kang, and R. A. Davis. Microsomal triglyceride transfer protein is essential for hepatic secretion of apoB-100 and apoB-48 but not triglyceride. J. Lipid Res. 2002. 43: 785–793.
Highlights
Despite a complete lack of microsomal triglyceride transfer protein (MTP), L35 rat hepatoma cells secrete triglyceride-containing lipoproteins, albeit at a rate 25% of that of parental FAO hepatoma cells, which express high levels of MTP
This oleic acid stimulation of [3H]triglyceride synthesis displayed by L35 cells was similar to the 32.4-fold increase displayed by FAO cells (Fig. 1B)
The findings showing that L35 cells secreted triglyceride at 25% the levels displayed by FAO cells (Fig. 4A) suggest that the MTP/apoB-independent pathway has a reduced capacity to secrete triglycerides compared with the MTP/apoB-dependent pathway
Summary
Despite a complete lack of microsomal triglyceride transfer protein (MTP), L35 rat hepatoma cells secrete triglyceride-containing lipoproteins, albeit at a rate 25% of that of parental FAO hepatoma cells, which express high levels of MTP. Since MTP deficiency in humans is associated with an almost complete absence of both apoB-100 and apoB-48 in the plasma [14], the findings showing that liver-specific MTP knockout caused only a slight reduction in plasma apoB-48 raised the possibility that MTP may not be essential for the secretion of apoB-48 in mice [22]. This interpretation has important implications in evaluating many studies of assembly and secretion of apoB-containing lipoproteins performed in mice and rats. Our data indicate that in rats MTP is required for the secretion of both apoB-100 and apoB-48
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