Microsomal triglyceride transfer protein is essential for hepatic secretion of apoB-100 and apoB-48 but not triglyceride.
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
To Yuen
TY
Cell and Molecular Biology Laboratory, Department of Biology, San Diego State University, San Diego, CA 92182, USA.
Olivier
Lisa M
LM
Kang
Sohye
S
Davis
Roger A
RA
D000818:Animals; D053299:Apolipoprotein B-100; D053283:Apolipoprotein B-48; D001055:Apolipoproteins B / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D008099:Liver / Q000378:metabolism*; D008114:Liver Neoplasms, Experimental; D008862:Microsomes, Liver / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011865:Radioisotope Dilution Technique; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection; D014280:Triglycerides / Q000378:metabolism; D014316:Tritium; D014407:Tumor Cells, Cultured
D053299:Apolipoprotein B-100; D053283:Apolipoprotein B-48; D001055:Apolipoproteins B; D002352:Carrier Proteins; D011994:Recombinant Proteins; D014280:Triglycerides; C106092:microsomal triglyceride transfer protein; D014316:Tritium