Back to Search
Start Over
Monocyte bioenergetics: An immunometabolic perspective in metabolic dysfunction-associated steatohepatitis.
- Source :
-
Cell reports. Medicine [Cell Rep Med] 2024 May 21; Vol. 5 (5), pp. 101564. Date of Electronic Publication: 2024 May 10. - Publication Year :
- 2024
-
Abstract
- Monocytes (Mos) are crucial in the evolution of metabolic dysfunction-associated steatotic liver disease (MASLD) to metabolic dysfunction-associated steatohepatitis (MASH), and immunometabolism studies have recently suggested targeting leukocyte bioenergetics in inflammatory diseases. Here, we reveal a peculiar bioenergetic phenotype in circulating Mos of patients with MASH, characterized by high levels of glycolysis and mitochondrial (mt) respiration. The enhancement of mt respiratory chain activity, especially complex II (succinate dehydrogenase [SDH]), is unbalanced toward the production of reactive oxygen species (ROS) and is sustained at the transcriptional level with the involvement of the AMPK-mTOR-PGC-1α axis. The modulation of mt activity with dimethyl malonate (DMM), an SDH inhibitor, restores the metabolic profile and almost abrogates cytokine production. Analysis of a public single-cell RNA sequencing (scRNA-seq) dataset confirms that in murine models of MASH, liver Mo-derived macrophages exhibit an upregulation of mt and glycolytic energy pathways. Accordingly, the DMM injection in MASH mice contrasts Mo infiltration and macrophagic enrichment, suggesting immunometabolism as a potential target in MASH.<br />Competing Interests: Declaration of interests The authors declare no competing interests.<br /> (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Humans
Animals
Mice
Fatty Liver metabolism
Fatty Liver pathology
Fatty Liver immunology
Male
Glycolysis
Reactive Oxygen Species metabolism
Mice, Inbred C57BL
Macrophages metabolism
Macrophages immunology
Female
Liver metabolism
Liver pathology
Energy Metabolism
Monocytes metabolism
Monocytes immunology
Mitochondria metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2666-3791
- Volume :
- 5
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Cell reports. Medicine
- Publication Type :
- Academic Journal
- Accession number :
- 38733988
- Full Text :
- https://doi.org/10.1016/j.xcrm.2024.101564