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Hepatic stellate cells retain the capacity to synthesize retinyl esters and to store neutral lipids in small lipid droplets in the absence of LRAT

Hepatic stellate cells (HSCs) play an important role in liver physiology and under healthy conditions they have a quiescent and lipid-storing phenotype. Upon liver injury, HSCs are activated and rapidly lose their retinyl ester-containing lipid droplets. To investigate the role of lecithin:retinol a...

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Main Authors: Md. Ajat, Mohd Mokrish, Molenaar, Martijn, Brouwers, Jos F. H. M., Vaandrager, Arie B., Houweling, Martin, Helms, J. Bernd
Format: Article
Language:English
Published: Elsevier 2017
Online Access:http://psasir.upm.edu.my/id/eprint/62023/1/Hepatic%20stellate%20cells%20retain%20.pdf
http://psasir.upm.edu.my/id/eprint/62023/
https://www.sciencedirect.com/science/article/pii/S1388198116303006?via%3Dihub#!
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spelling my.upm.eprints.620232019-03-18T04:23:34Z http://psasir.upm.edu.my/id/eprint/62023/ Hepatic stellate cells retain the capacity to synthesize retinyl esters and to store neutral lipids in small lipid droplets in the absence of LRAT Md. Ajat, Mohd Mokrish Molenaar, Martijn Brouwers, Jos F. H. M. Vaandrager, Arie B. Houweling, Martin Helms, J. Bernd Hepatic stellate cells (HSCs) play an important role in liver physiology and under healthy conditions they have a quiescent and lipid-storing phenotype. Upon liver injury, HSCs are activated and rapidly lose their retinyl ester-containing lipid droplets. To investigate the role of lecithin:retinol acyltransferase (LRAT) and acyl-CoA:diacylglycerol acyltransferase 1 (DGAT1) in retinyl ester synthesis and lipid droplet dynamics, we modified LC–MS/MS procedures by including multiple reaction monitoring allowing unambiguous identification and quantification of all major retinyl ester species. Quiescent primary HSCs contain predominantly retinyl palmitate. Exogenous fatty acids are a major determinant in the retinyl ester species synthesized by activated HSCs and LX-2 cells, indicating that HSCs shift their retinyl ester synthesizing capacity from LRAT to DGAT1 during activation. Quiescent LRAT−/− HSCs retain the capacity to synthesize retinyl esters and to store neutral lipids in lipid droplets ex vivo. The median lipid droplet size in LRAT−/− HSCs (1080 nm) is significantly smaller than in wild type HSCs (1618 nm). This is a consequence of an altered lipid droplet size distribution with 50.5 ± 9.0% small (≤ 700 nm) lipid droplets in LRAT−/− HSCs and 25.6 ± 1.4% large (1400–2100 nm) lipid droplets in wild type HSC cells. Upon prolonged (24 h) incubation, the amounts of small (≤ 700 nm) lipid droplets strongly increased both in wild type and in LRAT−/− HSCs, indicating a dynamic behavior in both cell types. The absence of retinyl esters and reduced number of lipid droplets in LRAT-deficient HSCs in vivo will be discussed. Elsevier 2017-02 Article PeerReviewed text en http://psasir.upm.edu.my/id/eprint/62023/1/Hepatic%20stellate%20cells%20retain%20.pdf Md. Ajat, Mohd Mokrish and Molenaar, Martijn and Brouwers, Jos F. H. M. and Vaandrager, Arie B. and Houweling, Martin and Helms, J. Bernd (2017) Hepatic stellate cells retain the capacity to synthesize retinyl esters and to store neutral lipids in small lipid droplets in the absence of LRAT. Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, 1862 (2). pp. 176-187. ISSN 1388-1981 https://www.sciencedirect.com/science/article/pii/S1388198116303006?via%3Dihub#! 10.1016/j.bbalip.2016.10.013
institution Universiti Putra Malaysia
building UPM Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Putra Malaysia
content_source UPM Institutional Repository
url_provider http://psasir.upm.edu.my/
language English
description Hepatic stellate cells (HSCs) play an important role in liver physiology and under healthy conditions they have a quiescent and lipid-storing phenotype. Upon liver injury, HSCs are activated and rapidly lose their retinyl ester-containing lipid droplets. To investigate the role of lecithin:retinol acyltransferase (LRAT) and acyl-CoA:diacylglycerol acyltransferase 1 (DGAT1) in retinyl ester synthesis and lipid droplet dynamics, we modified LC–MS/MS procedures by including multiple reaction monitoring allowing unambiguous identification and quantification of all major retinyl ester species. Quiescent primary HSCs contain predominantly retinyl palmitate. Exogenous fatty acids are a major determinant in the retinyl ester species synthesized by activated HSCs and LX-2 cells, indicating that HSCs shift their retinyl ester synthesizing capacity from LRAT to DGAT1 during activation. Quiescent LRAT−/− HSCs retain the capacity to synthesize retinyl esters and to store neutral lipids in lipid droplets ex vivo. The median lipid droplet size in LRAT−/− HSCs (1080 nm) is significantly smaller than in wild type HSCs (1618 nm). This is a consequence of an altered lipid droplet size distribution with 50.5 ± 9.0% small (≤ 700 nm) lipid droplets in LRAT−/− HSCs and 25.6 ± 1.4% large (1400–2100 nm) lipid droplets in wild type HSC cells. Upon prolonged (24 h) incubation, the amounts of small (≤ 700 nm) lipid droplets strongly increased both in wild type and in LRAT−/− HSCs, indicating a dynamic behavior in both cell types. The absence of retinyl esters and reduced number of lipid droplets in LRAT-deficient HSCs in vivo will be discussed.
format Article
author Md. Ajat, Mohd Mokrish
Molenaar, Martijn
Brouwers, Jos F. H. M.
Vaandrager, Arie B.
Houweling, Martin
Helms, J. Bernd
spellingShingle Md. Ajat, Mohd Mokrish
Molenaar, Martijn
Brouwers, Jos F. H. M.
Vaandrager, Arie B.
Houweling, Martin
Helms, J. Bernd
Hepatic stellate cells retain the capacity to synthesize retinyl esters and to store neutral lipids in small lipid droplets in the absence of LRAT
author_facet Md. Ajat, Mohd Mokrish
Molenaar, Martijn
Brouwers, Jos F. H. M.
Vaandrager, Arie B.
Houweling, Martin
Helms, J. Bernd
author_sort Md. Ajat, Mohd Mokrish
title Hepatic stellate cells retain the capacity to synthesize retinyl esters and to store neutral lipids in small lipid droplets in the absence of LRAT
title_short Hepatic stellate cells retain the capacity to synthesize retinyl esters and to store neutral lipids in small lipid droplets in the absence of LRAT
title_full Hepatic stellate cells retain the capacity to synthesize retinyl esters and to store neutral lipids in small lipid droplets in the absence of LRAT
title_fullStr Hepatic stellate cells retain the capacity to synthesize retinyl esters and to store neutral lipids in small lipid droplets in the absence of LRAT
title_full_unstemmed Hepatic stellate cells retain the capacity to synthesize retinyl esters and to store neutral lipids in small lipid droplets in the absence of LRAT
title_sort hepatic stellate cells retain the capacity to synthesize retinyl esters and to store neutral lipids in small lipid droplets in the absence of lrat
publisher Elsevier
publishDate 2017
url http://psasir.upm.edu.my/id/eprint/62023/1/Hepatic%20stellate%20cells%20retain%20.pdf
http://psasir.upm.edu.my/id/eprint/62023/
https://www.sciencedirect.com/science/article/pii/S1388198116303006?via%3Dihub#!
_version_ 1643837650122047488
score 13.211869

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