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

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

• Tipo de documento: Artigo Científico
• Fonte: ISCIENCE; v. 26, n. 10, p. 16-pg., 2023-10-20.

Resumo

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(hi)MHCII(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 charac-terized by elevated glycolysis, phagocytosis, and efferocytosis signatures. CX3CR1(hi)MHCII(hi) colonic resident LPMs had fewer lipid droplets (LDs) and decreased triacylglycerol (TG) content compared to equiv-alent cells in lean mice and exhibited increased phagocytic capacity, suggesting that HFD induces adaptive responses in LPMs to limit bacterial translocation. (AU)

• Processo FAPESP: 17/05264-7 - Metabolismo celular, microbiota e sistema imune: novos paradigmas na fisiopatologia das doenças renais
• Beneficiário: Niels Olsen Saraiva Câmara
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 15/18121-4 - Estudo da relação entre a obesidade e a função das células da lâmina própria intestinal no desenvolvimento da resistência à insulina
• Beneficiário: Angela Castoldi
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 17/00721-0 - Desvendando a demanda metabólica de macrófagos da lâmina própria intestinal e o seu papel no desenvolvimento da Obesidade e resistência à insulina
• Beneficiário: Angela Castoldi
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado