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Metabolic Adaptations and Functional Activity of Macrophages in Homeostasis and Inflammation

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Abstract

In recent years, the role of cellular metabolism in immunity has come into the focus of many studies. These processes form a basis for the maintenance of tissue integrity and homeostasis, as well as represent an integral part of the immune response, in particular, inflammation. Metabolic adaptations not only ensure energy supply for immune response, but also affect the functions of immune cells by controlling transcriptional and post-transcriptional programs. Studying the immune cell metabolism facilitates the search for new treatment approaches, especially for metabolic disorders. Macrophages, innate immune cells, are characterized by a high functional plasticity and play a key role in homeostasis and inflammation. Depending on the phenotype and origin, they can either perform various regulatory functions or promote inflammation state, thus exacerbating the pathological condition. Furthermore, their adaptations to the tissue-specific microenvironment influence the intensity and type of immune response. The review examines the effect of metabolic reprogramming in macrophages on the functional activity of these cells and their polarization. The role of immunometabolic adaptations of myeloid cells in tissue homeostasis and in various pathological processes in the context of inflammatory and metabolic diseases is specifically discussed. Finally, modulation of the macrophage metabolism-related mechanisms reviewed as a potential therapeutic approach.

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Abbreviations

2-DG:

2-deoxyglucose

2-HG:

2-hydroxyglutarate

ARG1:

arginase 1

ACLY:

ATP citrate lyase

AMPK:

AMP-activated protein kinase

CPT:

carnitine palmitoyltransferase

DMF:

dimethyl fumarate

ETC:

electron transport chain

FA:

fatty acid

HIF-1α:

hypoxia-inducible factor 1-alpha

IDH:

isocitrate dehydrogenase

iNOS:

inducible nitric oxide synthase

LDHA:

lactate dehydrogenase

LPS:

lipopolysaccharide

mTOR:

mammalian target of rapamycin

OXPHOS:

oxidative phosphorylation

PGE2 :

prostaglandin E2

PKM2:

pyruvate kinase M2

PPP:

pentose phosphate pathway

ROS:

reactive oxygen species

SDH:

succinate dehydrogenase

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Acknowledgments

The authors express their gratitude to D. Anisov for discussions and valuable remarks.

Funding

This work was supported by the Russian Science Foundation (project no. 19-75-30032).

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Authors and Affiliations

  1. Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991, Moscow, Russia

    Taisiya R. Yurakova, Ekaterina A. Gorshkova & Marina S. Drutskaya

  2. Trinity Biomedical Sciences Institute, Trinity College Dublin, D02F306, Dublin, Ireland

    Maxim A. Nosenko

  3. Division of Immunobiology and Biomedicine, Center of Genetics and Life Sciences, Sirius University of Science and Technology, 354340, Federal Territory Sirius, Russia

    Marina S. Drutskaya

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Contributions

M.S.D. supervised the study and developed the concept of the review; T.R.Y., E.A.G., and M.A.N. carried out the search of literature sources and discussed the data; T.R.Y. and M.A.N. prepared the manuscript; M.S.D. and E.A.G. edited the manuscript; T.R.Y. prepared the images.

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Correspondence to Marina S. Drutskaya.

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Yurakova, T.R., Gorshkova, E.A., Nosenko, M.A. et al. Metabolic Adaptations and Functional Activity of Macrophages in Homeostasis and Inflammation. Biochemistry Moscow 89, 817–838 (2024). https://doi.org/10.1134/S0006297924050043

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  • DOI: https://doi.org/10.1134/S0006297924050043

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