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Hepatic VLDL secretion: DGAT1 determines particle size but not particle number, which can be supported entirely by DGAT2
- Source :
- Journal of Lipid Research, Vol 60, Iss 1, Pp 111-120 (2019), Journal of Lipid Research
- Publication Year :
- 2019
- Publisher :
- Elsevier, 2019.
-
Abstract
- We investigated whether, in view of its activity being expressed on both aspects of the endoplasmic reticulum (ER; dual membrane topology), diacylglycerol acyltransferase 1 (DGAT1) plays a distinctive role in determining the triglyceride (TAG) content of VLDL particles secreted by the liver. Mice in which the DGAT1 gene was specifically ablated in hepatocytes (DGAT1-LKO mice) had the same number of VLDL particles (apoB concentration) in the plasma 1 h after Triton 1339 treatment, but these particles were approximately half the size of VLDL particles secreted by control mice and had a proportionately decreased content of TAG, with normal cholesterol and cholesteryl ester contents. Analyses of purified microsomal fractions prepared from 16 h fasted control and DAGT1-LKO mice showed that the TAG/protein ratio in the ER was significantly lower in the latter. Electron micrographs of these livers showed that those from DGAT1-LKO mice did not show the increased lipid content of the smooth ER shown by control livers. The effects of DGAT1- and DGAT2-specific inhibitors on apoB secretion by HepG2 cells showed that DGAT1 is not indispensable for apoB secretion and demonstrated redundancy in the ability of the two enzymes to support apoB secretion. Therefore, our findings show that DGAT1 is essential for the complete lipidation and maturation of VLDL particles within the lumen of the ER, consistent with its dual topology within the ER membrane. In the mouse, DGAT2 can support apoB secretion (particle number) even when TAG availability for full VLDL lipidation is restricted in the absence of DGAT1.
- Subjects :
- 0301 basic medicine
Very low-density lipoprotein
Apolipoprotein B
Lipid-anchored protein
030204 cardiovascular system & hematology
Lipoproteins, VLDL
Endoplasmic Reticulum
Biochemistry
chemistry.chemical_compound
Gene Knockout Techniques
Mice
0302 clinical medicine
Endocrinology
cardiovascular disease
QD
liver metabolism
triglycerides
Research Articles
diacylglycerol acyltransferase 1
biology
Hep G2 Cells
Cell biology
very low density lipoprotein
Liver
Membrane topology
Cholesteryl ester
lipids (amino acids, peptides, and proteins)
QD415-436
metabolic syndrome
Gene Expression Regulation, Enzymologic
03 medical and health sciences
Animals
Humans
Secretion
Diacylglycerol O-Acyltransferase
RNA, Messenger
Particle Size
Apolipoproteins B
QM
Endoplasmic reticulum
Lipogenesis
Cell Biology
QP
lipids and cholesterol
lipoproteins
030104 developmental biology
chemistry
biology.protein
Microsome
Hepatocytes
metabolism
RC
Subjects
Details
- Language :
- English
- ISSN :
- 00222275
- Volume :
- 60
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Journal of Lipid Research
- Accession number :
- edsair.doi.dedup.....b6af52e64234fe88c035736bd6cb4c79