Reversible expansion of tissue macrophages in response to macrophage colony-stimulating factor (CSF1) transforms systemic lipid and carbohydrate metabolism.

Autor:	Keshvari S; Mater Research Institute-The University of Queensland, Translational Research Institute, Brisbane, Queensland, Australia., Masson JJR; Mater Research Institute-The University of Queensland, Translational Research Institute, Brisbane, Queensland, Australia., Ferrari-Cestari M; Mater Research Institute-The University of Queensland, Translational Research Institute, Brisbane, Queensland, Australia., Bodea LG; Clem Jones Centre for Ageing and Dementia Research, Queensland Brain Institute, The University of Queensland, Brisbane, Queensland, Australia., Nooru-Mohamed F; Mater Research Institute-The University of Queensland, Translational Research Institute, Brisbane, Queensland, Australia., Tse BWC; Preclinical Imaging Facility, Translational Research Institute, Brisbane, Queensland, Australia., Sokolowski KA; Preclinical Imaging Facility, Translational Research Institute, Brisbane, Queensland, Australia., Batoon L; Mater Research Institute-The University of Queensland, Translational Research Institute, Brisbane, Queensland, Australia., Patkar OL; Mater Research Institute-The University of Queensland, Translational Research Institute, Brisbane, Queensland, Australia., Sullivan MA; Mater Research Institute-The University of Queensland, Translational Research Institute, Brisbane, Queensland, Australia., Ebersbach H; Novartis Institutes for Biomedical Research (NIBR), Basel, Switzerland., Stutz C; Novartis Institutes for Biomedical Research (NIBR), Basel, Switzerland., Parton RG; Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia.; Centre for Microscopy and Microanalysis, The University of Queensland, Brisbane, Queensland, Australia., Summers KM; Mater Research Institute-The University of Queensland, Translational Research Institute, Brisbane, Queensland, Australia., Pettit AR; Mater Research Institute-The University of Queensland, Translational Research Institute, Brisbane, Queensland, Australia., Hume DA; Mater Research Institute-The University of Queensland, Translational Research Institute, Brisbane, Queensland, Australia., Irvine KM; Mater Research Institute-The University of Queensland, Translational Research Institute, Brisbane, Queensland, Australia.
Jazyk:	angličtina
Zdroj:	American journal of physiology. Endocrinology and metabolism [Am J Physiol Endocrinol Metab] 2024 Feb 01; Vol. 326 (2), pp. E149-E165. Date of Electronic Publication: 2023 Dec 20.
DOI:	10.1152/ajpendo.00347.2023
Abstrakt:	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. NEW & NOTEWORTHY 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.
Databáze:	MEDLINE
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