PreprintArticleVersion 1This version is not peer-reviewed
Extensive Computational Screening Identifies Marco (SR-A6) and Abca1/2 as Key Regulators of Intracellular Lipid Metabolism to Compensate Low Cholesterol Biosynthesis in M1 Macrophages Hysteresis
Version 1
: Received: 1 November 2024 / Approved: 1 November 2024 / Online: 1 November 2024 (13:46:31 CET)
How to cite:
Zhang, Y.; Yang, W.; Kumagai, Y.; Martin, L.; Yang, Y.; Park, S.-J.; Nakai, K. Extensive Computational Screening Identifies Marco (SR-A6) and Abca1/2 as Key Regulators of Intracellular Lipid Metabolism to Compensate Low Cholesterol Biosynthesis in M1 Macrophages Hysteresis. Preprints2024, 2024110082. https://doi.org/10.20944/preprints202411.0082.v1
Zhang, Y.; Yang, W.; Kumagai, Y.; Martin, L.; Yang, Y.; Park, S.-J.; Nakai, K. Extensive Computational Screening Identifies Marco (SR-A6) and Abca1/2 as Key Regulators of Intracellular Lipid Metabolism to Compensate Low Cholesterol Biosynthesis in M1 Macrophages Hysteresis. Preprints 2024, 2024110082. https://doi.org/10.20944/preprints202411.0082.v1
Zhang, Y.; Yang, W.; Kumagai, Y.; Martin, L.; Yang, Y.; Park, S.-J.; Nakai, K. Extensive Computational Screening Identifies Marco (SR-A6) and Abca1/2 as Key Regulators of Intracellular Lipid Metabolism to Compensate Low Cholesterol Biosynthesis in M1 Macrophages Hysteresis. Preprints2024, 2024110082. https://doi.org/10.20944/preprints202411.0082.v1
APA Style
Zhang, Y., Yang, W., Kumagai, Y., Martin, L., Yang, Y., Park, S. J., & Nakai, K. (2024). Extensive Computational Screening Identifies Marco (SR-A6) and Abca1/2 as Key Regulators of Intracellular Lipid Metabolism to Compensate Low Cholesterol Biosynthesis in M1 Macrophages Hysteresis. Preprints. https://doi.org/10.20944/preprints202411.0082.v1
Chicago/Turabian Style
Zhang, Y., Sung-Joon Park and Kenta Nakai. 2024 "Extensive Computational Screening Identifies Marco (SR-A6) and Abca1/2 as Key Regulators of Intracellular Lipid Metabolism to Compensate Low Cholesterol Biosynthesis in M1 Macrophages Hysteresis" Preprints. https://doi.org/10.20944/preprints202411.0082.v1
Abstract
(1) Background: Macrophages undergo polarization, resulting in distinct phenotypes. These transitions, including de-/repolarization, lead to hysteresis, where cells retain genetic and epigenetic signatures of previous states, influencing macrophage function. We previously identified a set of interferon-stimulated genes (ISGs) associated with high lipid levels in macrophages that exhibited hysteresis following M1 polarization, suggesting potential alterations in lipid metabolism; (2) Results: In this study, we applied Weighted Gene Co-expression Network Analysis (WGCNA) and conducted comparative analyses on 162 RNA-seq samples from de-/repolarized and lipid-loaded macrophages, followed by functional exploration; (3) Results: Our results show that in M1 hysteresis, the sustained high expression of Marco and suppression of Abca1/2 reduced lipid efflux, leading to elevated intracellular lipid levels. This accumulation may compensate for reduced cholesterol biosynthesis and provide energy for sustained inflammatory responses and interferon signaling; (4) Conclusions: Our findings elucidate the relationship between M1 hysteresis and lipid metabolism, contributing to understanding the underlying mechanisms of macrophage hysteresis.
Biology and Life Sciences, Immunology and Microbiology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
