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ORIGINAL RESEARCH article

Front. Cardiovasc. Med.
Sec. Lipids in Cardiovascular Disease
Volume 11 - 2024 | doi: 10.3389/fcvm.2024.1436865

CD36 Restricts Lipid-Associated Macrophages Accumulation in White Adipose Tissues During Atherogenesis

Provisionally accepted
Jue Zhang Jue Zhang 1Jackie Chang Jackie Chang 1Vaya Chen Vaya Chen 1Mirza Beg Mirza Beg 1Lance Vick Lance Vick 2Dandan Wang Dandan Wang 2Ankan Gupta Ankan Gupta 2Yaxin Wang Yaxin Wang 1Ziyu Zhang Ziyu Zhang 1Wen Dai Wen Dai 1Mindy Kim Mindy Kim 1Shan Song Shan Song 3Duane Pereira Duane Pereira 4Ze Zheng Ze Zheng 2Komal Sodhi Komal Sodhi 4Joseph I. Shapiro Joseph I. Shapiro 2Roy L. Silverstein Roy L. Silverstein 2Subramaniam Malarkannan Subramaniam Malarkannan 1Yiliang Chen Yiliang Chen 2*
  • 1 Versiti Blood Research Institute, Milwaukee, Wisconsin, United States
  • 2 Medical College of Wisconsin, Milwaukee, United States
  • 3 Hebei Medical University, Shijiazhuang, Hebei Province, China
  • 4 Marshall University, Huntington, Indiana, United States

The final, formatted version of the article will be published soon.

    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.

    Keywords: Lipid, Inflammation, visceral adipose tissue, macrophage, ScRNA-seq, Atherosclerosis

    Received: 22 May 2024; Accepted: 01 Jul 2024.

    Copyright: © 2024 Zhang, Chang, Chen, Beg, Vick, Wang, Gupta, Wang, Zhang, Dai, Kim, Song, Pereira, Zheng, Sodhi, Shapiro, Silverstein, Malarkannan and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Yiliang Chen, Medical College of Wisconsin, Milwaukee, United States

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