Metabolic and functional remodeling of colonic macrophages in response to 
high-fat diet-induced obesity

Castoldi, Angela; Sanin, David E; van Bakker, Nikki Teijlingen; Aguiar, Cristhiane F; de Monteiro, Lauar Brito; Rana, Nisha; Grzes, Katarzyna M; Kabat, Agnieszka M; Curtis, Jonathan; Cameron, Alanna M; Caputa, George; de Souza, Tiago Antônio; Souto, Fabrício O; Büscher, Jörg Martin; Edwards-Hicks, Joy; Pearce, Erika Laine; Pearce, Edward Jonathen; Camara, Niels Olsen Saraiva

doi:10.1016/j.isci.2023.107719

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Metabolic and functional remodeling of colonic macrophages in response to high-fat diet-induced obesity

MPS-Authors

Castoldi, Angela
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Sanin, David E
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

van Bakker, Nikki Teijlingen
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

de Monteiro, Lauar Brito
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Rana, Nisha
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Grzes, Katarzyna M
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Kabat, Agnieszka M
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Curtis, Jonathan
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Cameron, Alanna M
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Caputa, George
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Büscher, Jörg Martin
Metabolomics Facility, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Edwards-Hicks, Joy
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Pearce, Erika Laine
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

/persons/resource/persons201435

Pearce, Edward Jonathen
Department Immunometabolism, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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https://www.sciencedirect.com/science/article/pii/S2589004223017960?via%3Dihub
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10.1016_j.isci.2023.107719.pdf
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Citation

Castoldi, A., Sanin, D. E., van Bakker, N. T., Aguiar, C. F., de Monteiro, L. B., Rana, N., et al. (2023). Metabolic and functional remodeling of colonic macrophages in response to high-fat diet-induced obesity. iScience, 26: 107719. doi:10.1016/j.isci.2023.107719.

Cite as: https://hdl.handle.net/21.11116/0000-000D-B6EE-A

Abstract

Little is known about the effects of high-fat diet (HFD)-induced obesity on resident colonic lamina propria (LP) macrophages (LPMs) function and metabolism. Here, we report that obesity and diabetes resulted in increased macrophage infiltration in the colon. These macrophages exhibited the residency phenotype CX3CR1^hiMHCII^hi and were CD4^-TIM4^-. During HFD, resident colonic LPM exhibited a lipid metabolism gene expression signature that overlapped that used to define lipid-associated macrophages (LAMs). Via single-cell RNA sequencing, we identified a sub-cluster of macrophages, increased in HFD, that were responsible for the LAM signature. Compared to other macrophages in the colon, these cells were characterized by elevated glycolysis, phagocytosis, and efferocytosis signatures. CX3CR1^hiMHCII^hi colonic resident LPMs had fewer lipid droplets (LDs) and decreased triacylglycerol (TG) content compared to equivalent cells in lean mice and exhibited increased phagocytic capacity, suggesting that HFD induces adaptive responses in LPMs to limit bacterial translocation.