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

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

doi:10.1016/j.isci.2023.107719

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

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

School of Medicine

Research output: Contribution to journal › Article › peer-review

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.

Original language	English (US)
Article number	107719
Journal	iScience
Volume	26
Issue number	10
DOIs	https://doi.org/10.1016/j.isci.2023.107719
State	Published - Oct 20 2023

Keywords

Endocrinology
Immune response
Metabolomics

ASJC Scopus subject areas

General

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10.1016/j.isci.2023.107719

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Castoldi, A., Sanin, D. E., van Teijlingen Bakker, N., Aguiar, C. F., de Brito Monteiro, L., Rana, N., Grzes, K. M., Kabat, A. M., Curtis, J., Cameron, A. M., Caputa, G., Antônio de Souza, T., Souto, F. O., Buescher, J. M., Edwards-Hicks, J., Pearce, E. L., Pearce, E. J., & Saraiva Camara, N. O. (2023). Metabolic and functional remodeling of colonic macrophages in response to high-fat diet-induced obesity. iScience, 26(10), Article 107719. https://doi.org/10.1016/j.isci.2023.107719

Castoldi, A, Sanin, DE, van Teijlingen Bakker, N, Aguiar, CF, de Brito Monteiro, L, Rana, N, Grzes, KM, Kabat, AM, Curtis, J, Cameron, AM, Caputa, G, Antônio de Souza, T, Souto, FO, Buescher, JM, Edwards-Hicks, J, Pearce, EL , Pearce, EJ & Saraiva Camara, NO 2023, 'Metabolic and functional remodeling of colonic macrophages in response to high-fat diet-induced obesity', iScience, vol. 26, no. 10, 107719. https://doi.org/10.1016/j.isci.2023.107719

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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 CX3CR1hiMHCIIhi 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. CX3CR1hiMHCIIhi 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.",

keywords = "Endocrinology, Immune response, Metabolomics",

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AU - Aguiar, Cristhiane F.

AU - de Brito Monteiro, Lauar

AU - Rana, Nisha

AU - Grzes, Katarzyna M.

AU - Kabat, Agnieszka M.

AU - Curtis, Jonathan

AU - Cameron, Alanna M.

AU - Caputa, George

AU - Antônio de Souza, Tiago

AU - Souto, Fabrício O.

AU - Buescher, Joerg M.

AU - Edwards-Hicks, Joy

AU - Pearce, Erika L.

AU - Pearce, Edward J.

AU - Saraiva Camara, Niels Olsen

PY - 2023/10/20

Y1 - 2023/10/20

N2 - 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 CX3CR1hiMHCIIhi 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. CX3CR1hiMHCIIhi 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.

AB - 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 CX3CR1hiMHCIIhi 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. CX3CR1hiMHCIIhi 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.

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

Abstract

Keywords

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