Role of Tim4 in the regulation of ABCA1+ adipose tissue macrophages and post-prandial cholesterol levels
| Autor: | Roland H Stimson, Neil Henderson, Marc R. Dweck, Cécile Bénézech, Zoi Michalidou, Calum C. Bain, Stephen J. Jenkins, Prakash Ramachandran, Laura Denby, Lucy H. Jackson-Jones, Marlene Magalhaes, Jordan R. Portman, Pete Smith |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Vesicular Transport Proteins General Physics and Astronomy Adipose tissue 030204 cardiovascular system & hematology Mice chemistry.chemical_compound 0302 clinical medicine High-density lipoprotein Macrophage education.field_of_study Multidisciplinary biology digestive oral and skin physiology Postprandial Period Cholesterol Adipose Tissue lipids (amino acids peptides and proteins) Fat metabolism ATP Binding Cassette Transporter 1 Transcriptional Activation medicine.medical_specialty Adipose tissue macrophages Science Population Diet High-Fat Article General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Internal medicine medicine Animals Obesity education Monocytes and macrophages Dyslipidaemias Macrophages Cholesterol HDL Membrane Proteins Lipid metabolism General Chemistry Lipid Metabolism 030104 developmental biology Endocrinology chemistry ABCA1 biology.protein Lysosomes |
| Zdroj: | Nature Communications, Vol 12, Iss 1, Pp 1-15 (2021) Nature Communications Magalhaes, M S, Smith, P, Portman, J, Jackson-Jones, L H, Bain, C C, Ramachandran, P, Michailidou, Z, Stimson, R H, Dweck, M R, Denby, L, Henderson, N C, Jenkins, S J & Benezech, C 2021, ' Role of Tim4 in the regulation of ABCA1+ adipose tissue macrophages and post-prandial cholesterol levels ', Nature Communications . https://doi.org/10.1038/s41467-021-24684-7 |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-021-24684-7 |
| Popis: | 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. Diverse macrophage subsets are found in adipose tissue where they regulate its physiology. Here, the authors used single-cell RNA sequencing to analyse the effect of post-prandial lipids on adipose tissue macrophages and identify Tim4 as a regulator of ABCA1+ macrophage function and post-prandial cholesterol transport. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink