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Microsomal triglyceride transfer protein is essential for hepatic secretion of apoB-100 and apoB-48 but not
To Yuen Hui1, Lisa M Olivier, Sohye Kang
1Cell and Molecular Biology Laboratory, Department of Biology, San Diego State University, San Diego, CA 92182, USA.
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.
Insights
Microsomal triglyceride transfer protein (MTP) is essential for secreting lipoproteins containing apolipoprotein B (apoB). However, some cells secrete triglyceride-rich lipoproteins via an MTP-independent pathway, suggesting a novel mechanism for lipid transport.
Area of Science:
- Lipid metabolism and lipoprotein assembly
- Cellular biology of hepatoma cells
- Biochemistry of apolipoproteins and MTP
Background:
- Microsomal triglyceride transfer protein (MTP) plays a crucial role in lipoprotein assembly and secretion.
- Apolipoprotein B (apoB) is essential for the formation of triglyceride-rich lipoproteins.
- L35 rat hepatoma cells lack MTP expression, offering a model to study MTP-independent pathways.
Purpose of the Study:
- To investigate the role of MTP in apolipoprotein B (apoB) secretion and triglyceride-rich lipoprotein assembly.
- To determine if MTP-deficient cells can secrete triglycerides via an alternative pathway.
- To characterize the composition of lipoproteins secreted by MTP-deficient cells.
Main Methods:
- Utilized L35 (MTP-deficient) and FAO (MTP-expressing) rat hepatoma cells.
- Assessed lipoprotein secretion with and without MTP expression (transgene) and MTP inhibition (BMS-200150).
- Analyzed the composition of secreted lipoproteins, including apolipoproteins (apoB-100, apoB-48, apoA-IV, apoE) and triglycerides.
Main Results:
- L35 cells secreted triglyceride-containing lipoproteins despite lacking MTP and apoB secretion.
- MTP expression restored apoB-100 and apoB-48 secretion in L35 cells.
- MTP inhibition significantly reduced triglyceride secretion in FAO cells but not L35 cells.
- Lipoproteins secreted by L35 cells were HDL-associated, containing apoA-IV and apoE, but devoid of apoB.
Conclusions:
- MTP is essential for apoB secretion, but triglyceride-rich lipoproteins can be secreted via an MTP- and apoB-independent pathway.
- This alternative pathway involves HDL-like particles containing apoA-IV and apoE.
- Findings suggest co-evolution of apoB and MTP to enhance triglyceride secretion through large, lipid-rich lipoproteins.
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