دورية أكاديمية
أعرض في EDS

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

التفاصيل البيبلوغرافية
العنوان: Role of Tim4 in the regulation of ABCA1 + adipose tissue macrophages and post-prandial cholesterol levels.
المؤلفون: Magalhaes MS; Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK., Smith P; Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK., Portman JR; Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK., Jackson-Jones LH; Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK.; Division of Biomedical and Life Sciences, Lancaster University, Lancaster, UK., Bain CC; Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK., Ramachandran P; Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK., Michailidou Z; Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK., Stimson RH; Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK., Dweck MR; Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK., Denby L; Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK., Henderson NC; Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK.; MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK., Jenkins SJ; Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK., Bénézech C; Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK. cbenezec@ed.ac.uk.
المصدر: Nature communications [Nat Commun] 2021 Jul 21; Vol. 12 (1), pp. 4434. Date of Electronic Publication: 2021 Jul 21.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [London] : Nature Pub. Group
مواضيع طبية MeSH: ATP Binding Cassette Transporter 1/*metabolism , Adipose Tissue/*metabolism , Cholesterol/*metabolism , Macrophages/*metabolism , Membrane Proteins/*metabolism , Postprandial Period/*physiology, Adipose Tissue/cytology ; Animals ; Cholesterol, HDL/metabolism ; Diet, High-Fat ; Lipid Metabolism ; Lysosomes/metabolism ; Macrophages/cytology ; Mice ; Obesity/metabolism ; Obesity/pathology ; Transcriptional Activation ; Vesicular Transport Proteins/metabolism
مستخلص: 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.
(© 2021. The Author(s).)
التعليقات: Erratum in: Nat Commun. 2022 Mar 25;13(1):1716. (PMID: 35338154)
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معلومات مُعتمدة: MR/N008340/1 United Kingdom MRC_ Medical Research Council; FS/14/78/31020 United Kingdom BHF_ British Heart Foundation; 219542/Z/19/Z United Kingdom WT_ Wellcome Trust; SCAF/17/02 United Kingdom CSO_ Chief Scientist Office; MR/L008076/1 United Kingdom MRC_ Medical Research Council; MR/M011542/1 United Kingdom MRC_ Medical Research Council; United Kingdom WT_ Wellcome Trust
المشرفين على المادة: 0 (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)
97C5T2UQ7J (Cholesterol)
تواريخ الأحداث: Date Created: 20210722 Date Completed: 20210802 Latest Revision: 20220401
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC8295389
DOI: 10.1038/s41467-021-24684-7
PMID: 34290249
قاعدة البيانات: MEDLINE
الوصف
تدمد:2041-1723
DOI:10.1038/s41467-021-24684-7