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CD36 restricts lipid-associated macrophages accumulation in white adipose tissues during atherogenesis

Authors :
Vaya Chen
Jue Zhang
Jackie Chang
Mirza Ahmar Beg
Lance Vick
Dandan Wang
Ankan Gupta
Yaxin Wang
Ziyu Zhang
Wen Dai
Mindy Kim
Shan Song
Duane Pereira
Ze Zheng
Komal Sodhi
Joseph I. Shapiro
Roy L. Silverstein
Subramaniam Malarkannan
Yiliang Chen
Source :
Frontiers in Cardiovascular Medicine, Vol 11 (2024)
Publication Year :
2024
Publisher :
Frontiers Media S.A., 2024.

Abstract

Visceral white adipose tissues (WAT) regulate systemic lipid metabolism and inflammation. Dysfunctional WAT drive chronic inflammation and facilitate atherosclerosis. Adipose tissue-associated macrophages (ATM) are the predominant immune cells in WAT, but their heterogeneity and phenotypes are poorly defined during atherogenesis. The scavenger receptor CD36 mediates ATM crosstalk with other adipose tissue cells, driving chronic inflammation. Here, we combined the single-cell RNA sequencing technique with cell metabolic and functional assays on major WAT ATM subpopulations using a diet-induced atherosclerosis mouse model (Apoe-null). We also examined the role of CD36 using Apoe/Cd36 double-null mice. Based on transcriptomics data and differential gene expression analysis, we identified a previously undefined group of ATM displaying low viability and high lipid metabolism and labeled them as “unhealthy macrophages”. Their phenotypes suggest a subpopulation of ATM under lipid stress. We also identified lipid-associated macrophages (LAM), which were previously described in obesity. Interestingly, LAM increased 8.4-fold in Apoe/Cd36 double-null mice on an atherogenic diet, but not in Apoe-null mice. The increase in LAM was accompanied by more ATM lipid uptake, reduced adipocyte hypertrophy, and less inflammation. In conclusion, CD36 mediates a delicate balance between lipid metabolism and inflammation in visceral adipose tissues. Under atherogenic conditions, CD36 deficiency reduces inflammation and increases lipid metabolism in WAT by promoting LAM accumulation.

Details

Language :
English
ISSN :
2297055X
Volume :
11
Database :
Directory of Open Access Journals
Journal :
Frontiers in Cardiovascular Medicine
Publication Type :
Academic Journal
Accession number :
edsdoj.b90896f82e094d6d9beb0115dbf0c24d
Document Type :
article
Full Text :
https://doi.org/10.3389/fcvm.2024.1436865