Triacylglycerol synthesis directed by glycerol-3-phosphate acyltransferases -3 and -4 is required for lipid droplet formation and the modulation of the inflammatory response during macrophage to foam cell transition.
Glycerolipids
Lipid droplets
Oxidized LDL
Journal
Atherosclerosis
ISSN: 1879-1484
Titre abrégé: Atherosclerosis
Pays: Ireland
ID NLM: 0242543
Informations de publication
Date de publication:
01 2021
01 2021
Historique:
received:
05
03
2020
revised:
21
10
2020
accepted:
19
11
2020
pubmed:
2
12
2020
medline:
24
6
2021
entrez:
1
12
2020
Statut:
ppublish
Résumé
The transition of macrophage to foam cells is a major hallmark of early stage atherosclerotic lesions. This process is characterized by the accumulation of large cytoplasmic lipid droplets containing large quantities of cholesterol esters (CE), triacylglycerol (TAG) and phospholipid (PL). Although cholesterol and CE metabolism during foam cell formation has been broadly studied, little is known about the role of the glycerolipids (TAG and PL) in this context. Here we studied the contribution of glycerolipid synthesis to lipid accumulation, focusing specifically on the first and rate-limiting enzyme of the pathway: glycerol-3-phosphate acyltransferase (GPAT). We used RAW 264.7 cells and bone marrow derived macrophages (BMDM) treated with oxidized LDL (oxLDL). We showed that TAG synthesis is induced during the macrophage to foam cell transition. The expression and activity of GPAT3 and GPAT4 also increased during this process, and these two isoforms were required for the accumulation of cell TAG and PL. Compared to cells from wildtype mice after macrophage to foam cell transition, Gpat4 Our results provide evidence that TAG synthesis directed by GPAT3 and GPAT4 is required for lipid droplet formation and the modulation of the inflammatory response during the macrophage-foam cell transition.
Sections du résumé
BACKGROUND AND AIMS
The transition of macrophage to foam cells is a major hallmark of early stage atherosclerotic lesions. This process is characterized by the accumulation of large cytoplasmic lipid droplets containing large quantities of cholesterol esters (CE), triacylglycerol (TAG) and phospholipid (PL). Although cholesterol and CE metabolism during foam cell formation has been broadly studied, little is known about the role of the glycerolipids (TAG and PL) in this context. Here we studied the contribution of glycerolipid synthesis to lipid accumulation, focusing specifically on the first and rate-limiting enzyme of the pathway: glycerol-3-phosphate acyltransferase (GPAT).
METHODS
We used RAW 264.7 cells and bone marrow derived macrophages (BMDM) treated with oxidized LDL (oxLDL).
RESULTS
We showed that TAG synthesis is induced during the macrophage to foam cell transition. The expression and activity of GPAT3 and GPAT4 also increased during this process, and these two isoforms were required for the accumulation of cell TAG and PL. Compared to cells from wildtype mice after macrophage to foam cell transition, Gpat4
CONCLUSIONS
Our results provide evidence that TAG synthesis directed by GPAT3 and GPAT4 is required for lipid droplet formation and the modulation of the inflammatory response during the macrophage-foam cell transition.
Identifiants
pubmed: 33260006
pii: S0021-9150(20)31531-8
doi: 10.1016/j.atherosclerosis.2020.11.022
pmc: PMC7803380
mid: NIHMS1650137
pii:
doi:
Substances chimiques
Lipoproteins, LDL
0
Phosphates
0
Triglycerides
0
Glycerol-3-Phosphate O-Acyltransferase
EC 2.3.1.15
1-Acylglycerol-3-Phosphate O-Acyltransferase
EC 2.3.1.51
GPAT3 protein, mouse
EC 2.3.1.51
Glycerol
PDC6A3C0OX
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1-7Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK056598
Pays : United States
Informations de copyright
Copyright © 2020 Elsevier B.V. All rights reserved.