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Lysophosphatidylcholine acyltransferase 3 knockdown-mediated liver lysophosphatidylcholine accumulation promotes very low density lipoprotein production by enhancing microsomal triglyceride transfer protein expression
- Source :
- The Journal of biological chemistry. 287(24)
- Publication Year :
- 2012
-
Abstract
- After de novo biosynthesis phospholipids undergo extensive remodeling by the Lands' cycle. Enzymes involved in phospholipid biosynthesis have been studied extensively but not those involved in reacylation of lysophosphopholipids. One key enzyme in the Lands' cycle is fatty acyl-CoA:lysophosphatidylcholine acyltransferase (LPCAT), which utilizes lysophosphatidylcholine (LysoPC) and fatty acyl-CoA to produce various phosphatidylcholine (PC) species. Four isoforms of LPCAT have been identified. In this study we found that LPCAT3 is the major hepatic isoform, and its knockdown significantly reduces hepatic LPCAT activity. Moreover, we report that hepatic LPCAT3 knockdown increases certain species of LysoPCs and decreases certain species of PC. A surprising observation was that LPCAT3 knockdown significantly reduces hepatic triglycerides. Despite this, these mice had higher plasma triglyceride and apoB levels. Lipoprotein production studies indicated that reductions in LPCAT3 enhanced assembly and secretion of triglyceride-rich apoB-containing lipoproteins. Furthermore, these mice had higher microsomal triglyceride transfer protein (MTP) mRNA and protein levels. Mechanistic studies in hepatoma cells revealed that LysoPC enhances secretion of apoB but not apoA-I in a concentration-dependent manner. Moreover, LysoPC increased MTP mRNA, protein, and activity. In short, these results indicate that hepatic LPCAT3 modulates VLDL production by regulating LysoPC levels and MTP expression.
- Subjects :
- Male
Very low-density lipoprotein
Apolipoprotein B
Lipoproteins, VLDL
Biochemistry
Microsomal triglyceride transfer protein
chemistry.chemical_compound
Mice
Phosphatidylcholine
Protein biosynthesis
Animals
RNA, Messenger
Molecular Biology
Triglycerides
Apolipoproteins B
Gene knockdown
biology
Apolipoprotein A-I
1-Acylglycerophosphocholine O-Acyltransferase
Lysophosphatidylcholines
Cell Biology
Lipids
Lysophosphatidylcholine
chemistry
Gene Expression Regulation
Liver
Gene Knockdown Techniques
Protein Biosynthesis
Apolipoprotein B-100
biology.protein
lipids (amino acids, peptides, and proteins)
Carrier Proteins
Lipoprotein
Subjects
Details
- ISSN :
- 1083351X
- Volume :
- 287
- Issue :
- 24
- Database :
- OpenAIRE
- Journal :
- The Journal of biological chemistry
- Accession number :
- edsair.doi.dedup.....d12b807f23ab1443fb2d832cfd4f2bd0