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Role of Tim4 in the regulation of ABCA1+ adipose tissue macrophages and post-prandial cholesterol levels

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Role of Tim4 in the regulation of ABCA1+ adipose tissue macrophages and post-prandial cholesterol levels. / Magalhaes, Marlene ; Smith, Peter; Portman, Jordan et al.
In: Nature Communications, Vol. 12, 4434, 21.07.2021.

Research output: Contribution to Journal/MagazineJournal articlepeer-review

Harvard

Magalhaes, M, Smith, P, Portman, J, Jackson-Jones, L, Bain, C, Ramachandran, P, Michalidou, Z, Stimson, R, Dweck, M, Denby, L, Henderson, N, Jenkins, S & Benezech, C 2021, 'Role of Tim4 in the regulation of ABCA1+ adipose tissue macrophages and post-prandial cholesterol levels', Nature Communications, vol. 12, 4434. https://doi.org/https://www.nature.com/articles/s41467-021-24684-7, https://doi.org/10.1038/s41467-021-24684-7

APA

Magalhaes, M., Smith, P., Portman, J., Jackson-Jones, L., Bain, C., Ramachandran, P., Michalidou, Z., Stimson, R., Dweck, M., Denby, L., Henderson, N., Jenkins, S., & Benezech, C. (2021). Role of Tim4 in the regulation of ABCA1+ adipose tissue macrophages and post-prandial cholesterol levels. Nature Communications, 12, Article 4434. https://doi.org/https://www.nature.com/articles/s41467-021-24684-7, https://doi.org/10.1038/s41467-021-24684-7

Vancouver

Magalhaes M, Smith P, Portman J, Jackson-Jones L, Bain C, Ramachandran P et al. Role of Tim4 in the regulation of ABCA1+ adipose tissue macrophages and post-prandial cholesterol levels. Nature Communications. 2021 Jul 21;12:4434. doi: https://www.nature.com/articles/s41467-021-24684-7, 10.1038/s41467-021-24684-7

Author

Magalhaes, Marlene ; Smith, Peter ; Portman, Jordan et al. / Role of Tim4 in the regulation of ABCA1+ adipose tissue macrophages and post-prandial cholesterol levels. In: Nature Communications. 2021 ; Vol. 12.

Bibtex

@article{3ede549203504174a4e57878aa69778e,
title = "Role of Tim4 in the regulation of ABCA1+ adipose tissue macrophages and post-prandial cholesterol levels",
abstract = "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+ resident adipose tissue macrophages in this process. Thus, these data indicate that Tim4 is a key regulator of post-prandial cholesterol transport and adipose tissue macrophage function and may represent a novel pathway to treat dyslipidemia.",
author = "Marlene Magalhaes and Peter Smith and Jordan Portman and Lucy Jackson-Jones and Calum Bain and Prakash Ramachandran and Zoi Michalidou and Roland Stimson and Marc Dweck and Laura Denby and Neil Henderson and Stephen Jenkins and Cecile Benezech",
year = "2021",
month = jul,
day = "21",
doi = "https://www.nature.com/articles/s41467-021-24684-7",
language = "English",
volume = "12",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",

}

RIS

TY - JOUR

T1 - Role of Tim4 in the regulation of ABCA1+ adipose tissue macrophages and post-prandial cholesterol levels

AU - Magalhaes, Marlene

AU - Smith, Peter

AU - Portman, Jordan

AU - Jackson-Jones, Lucy

AU - Bain, Calum

AU - Ramachandran, Prakash

AU - Michalidou, Zoi

AU - Stimson, Roland

AU - Dweck, Marc

AU - Denby, Laura

AU - Henderson, Neil

AU - Jenkins, Stephen

AU - Benezech, Cecile

PY - 2021/7/21

Y1 - 2021/7/21

N2 - 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+ resident adipose tissue macrophages in this process. Thus, these data indicate that Tim4 is a key regulator of post-prandial cholesterol transport and adipose tissue macrophage function and may represent a novel pathway to treat dyslipidemia.

AB - 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+ resident adipose tissue macrophages in this process. Thus, these data indicate that Tim4 is a key regulator of post-prandial cholesterol transport and adipose tissue macrophage function and may represent a novel pathway to treat dyslipidemia.

U2 - https://www.nature.com/articles/s41467-021-24684-7

DO - https://www.nature.com/articles/s41467-021-24684-7

M3 - Journal article

VL - 12

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 4434

ER -