Role of Tim4 in the regulation of ABCA1
ATP Binding Cassette Transporter 1
/ metabolism
Adipose Tissue
/ cytology
Animals
Cholesterol
/ metabolism
Cholesterol, HDL
/ metabolism
Diet, High-Fat
Lipid Metabolism
Lysosomes
/ metabolism
Macrophages
/ cytology
Membrane Proteins
/ metabolism
Mice
Obesity
/ metabolism
Postprandial Period
/ physiology
Transcriptional Activation
Vesicular Transport Proteins
/ metabolism
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
21 07 2021
21 07 2021
Historique:
received:
18
05
2020
accepted:
01
07
2021
entrez:
22
7
2021
pubmed:
23
7
2021
medline:
3
8
2021
Statut:
epublish
Résumé
Dyslipidemia is a main driver of cardiovascular diseases. The ability of macrophages to scavenge excess lipids implicate them as mediators in this process and understanding the mechanisms underlying macrophage lipid metabolism is key to the development of new treatments. Here, we investigated how adipose tissue macrophages regulate post-prandial cholesterol transport. Single-cell RNA sequencing and protected bone marrow chimeras demonstrated that ingestion of lipids led to specific transcriptional activation of a population of resident macrophages expressing Lyve1, Tim4, and ABCA1. Blocking the phosphatidylserine receptor Tim4 inhibited lysosomal activation and the release of post-prandial high density lipoprotein cholesterol following a high fat meal. Both effects were recapitulated by chloroquine, an inhibitor of lysosomal function. Moreover, clodronate-mediated cell-depletion implicated Tim4
Identifiants
pubmed: 34290249
doi: 10.1038/s41467-021-24684-7
pii: 10.1038/s41467-021-24684-7
pmc: PMC8295389
doi:
Substances chimiques
ABCA1 protein, mouse
0
ATP Binding Cassette Transporter 1
0
Cholesterol, HDL
0
LYVE1 protein, mouse
0
Membrane Proteins
0
TIM-4 protein, mouse
0
Vesicular Transport Proteins
0
Cholesterol
97C5T2UQ7J
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4434Subventions
Organisme : Medical Research Council
ID : MR/N008340/1
Pays : United Kingdom
Organisme : British Heart Foundation
ID : FS/14/78/31020
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 219542/Z/19/Z
Pays : United Kingdom
Organisme : Chief Scientist Office
ID : SCAF/17/02
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/L008076/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/M011542/1
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2021. The Author(s).
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