The Library
Hepatic VLDL secretion : DGAT1 determines particle size but not particle number, which can be supported entirely by DGAT2
Tools
Tools
Tools
Irshad, Zehra, Chmel, Nikola Paul, Adya, Raghu and Zammit, Victor A. (2019) Hepatic VLDL secretion : DGAT1 determines particle size but not particle number, which can be supported entirely by DGAT2. Journal of Lipid Research, 60 . pp. 111-120. doi:10.1194/jlr.M089300 ISSN 0022-2275.
![[img]](https://wrap.warwick.ac.uk/style/images/fileicons/application_pdf.png) |
PDF
WRAP-Hepatic-VLDL-secretion-DGAT1-determines-particle-size-Zammit-2018.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons Attribution 4.0. Download (1074Kb) |
|
PDF
WRAP-Hepatic-VLDL-secretion-determines-particle-size-particle-Zammit-2018.pdf - Accepted Version Embargoed item. Restricted access to Repository staff only - Requires a PDF viewer. Download (843Kb) |
Official URL: https://doi.org/10.1194/jlr.M089300
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.
| Item Type: | Journal Article | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| Subjects: | Q Science > QD Chemistry Q Science > QM Human anatomy Q Science > QP Physiology R Medicine > RC Internal medicine |
||||||||
| Divisions: | Faculty of Science, Engineering and Medicine > Science > Chemistry Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
||||||||
| Library of Congress Subject Headings (LCSH): | Triglycerides, Lipoproteins, Liver -- Metabolism, Cardiovascular system -- Diseases , Metabolic syndrome , Diglycerides | ||||||||
| Journal or Publication Title: | Journal of Lipid Research | ||||||||
| Publisher: | American Society for Biochemistry and Molecular Biology, Inc. | ||||||||
| ISSN: | 0022-2275 | ||||||||
| Official Date: | 31 January 2019 | ||||||||
| Dates: |
|
||||||||
| Volume: | 60 | ||||||||
| Page Range: | pp. 111-120 | ||||||||
| DOI: | 10.1194/jlr.M089300 | ||||||||
| Status: | Peer Reviewed | ||||||||
| Publication Status: | Published | ||||||||
| Reuse Statement (publisher, data, author rights): | This research was originally published in the Journal of Lipid Research. Irshad, Zehra, Chmel, Nikola Paul, Adya, Raghu and Zammit, Victor A. (2019) Hepatic VLDL secretion: DGAT1 determines particle size but not particle number, which can be supported entirely by DGAT2. Journal of Lipid Research, 60 . pp. 111-120. doi:10.1194/jlr.M089300 © the American Society for Biochemistry and Molecular Biology | ||||||||
| Access rights to Published version: | Open Access (Creative Commons) | ||||||||
| Date of first compliant deposit: | 13 November 2018 | ||||||||
| Date of first compliant Open Access: | 10 January 2019 | ||||||||
| RIOXX Funder/Project Grant: |
|
||||||||
| Related URLs: |
Request changes or add full text files to a record
Repository staff actions (login required)
 |
View Item |
Downloads
Downloads per month over past year
