Journal article
Reversible expansion of tissue macrophages in response to macrophage colony-stimulating factor (CSF1) transforms systemic lipid and carbohydrate metabolism
American Journal of Physiology: Endocrinology and Metabolism, Vol.326(2), pp.E149-E165
2024
PMID: 38117267
Abstract
Macrophages regulate metabolic homeostasis in health and disease. Macrophage colony-stimulating factor (CSF1)-dependent macrophages contribute to homeostatic control of the size of the liver. This study aimed to determine the systemic metabolic consequences of elevating circulating CSF1. Acute administration of a CSF1-Fc fusion protein to mice led to monocytosis, increased resident tissue macrophages in the liver and all major organs, and liver growth. These effects were associated with increased hepatic glucose uptake and extensive mobilization of body fat. The impacts of CSF1 on macrophage abundance, liver size, and body composition were rapidly reversed to restore homeostasis. The effects of CSF1 on metabolism were independent of several known endocrine regulators and did not impact the physiological fasting response. Analysis using implantable telemetry in metabolic cages revealed progressively reduced body temperature and physical activity with no change in diurnal food intake. These results demonstrate the existence of a dynamic equilibrium between CSF1, the mononuclear phagocyte system, and control of liver-to-body weight ratio, which in turn controls systemic metabolic homeostasis. This novel macrophage regulatory axis has the potential to promote fat mobilization, without changes in appetence, which may have novel implications for managing metabolic syndrome.
CSF1 administration expands tissue macrophages, which transforms systemic metabolism. CSF1 drives fat mobilization and glucose uptake to support liver growth. The effects of CSF1 are independent of normal hormonal metabolic regulation. The effects of CSF1 are rapidly reversible, restoring homeostatic body composition. CSF1-dependent macrophages and liver size are coupled in a dynamic equilibrium.
Details
- Title
- Reversible expansion of tissue macrophages in response to macrophage colony-stimulating factor (CSF1) transforms systemic lipid and carbohydrate metabolism
- Authors
- Sahar Keshvari - University of QueenslandJesse J R Masson - Mater ResearchMichelle Ferrari-Cestari - Mater ResearchLiviu-Gabriel Bodea - University of QueenslandFathima Nooru-Mohamed - University of QueenslandBrian Wan-Chi Tse - Translational Research InstituteKamil Sokolowski - Translational Research InstituteOmkar L Patkar - Translational Research InstituteMitchell A Sullivan - University of QueenslandHilmar Ebersbach - NovartisCian Stutz - NovartisRobert G Parton - University of QueenslandKim M Summers - Mater ResearchAllison R Pettit - Translational Research InstituteDavid A Hume - Translational Research InstituteKatherine M Irvine (Corresponding Author) - University of Queensland
- Publication details
- American Journal of Physiology: Endocrinology and Metabolism, Vol.326(2), pp.E149-E165
- Publisher
- American Physiological Society
- DOI
- 10.1152/ajpendo.00347.2023
- ISSN
- 1522-1555
- PMID
- 38117267
- Data Availability
- Metabolomics data are available at https://doi.org/10.21228/ M8TQ5G.
- Organisation Unit
- School of Health - Biomedicine
- Language
- English
- Record Identifier
- 991035092602621
- Output Type
- Journal article
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- Web Of Science research areas
- Endocrinology & Metabolism
- Physiology
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